Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The cytoplasmic dynein transport machinery and its many cargoes

Nature Reviews Molecular Cell Biology volume 19, pages 382–398 (2018)Cite this article

Subjects

A Publisher Correction to this article was published on 08 May 2018

This article has been updated

Abstract

Cytoplasmic dynein 1 is an important microtubule-based motor in many eukaryotic cells. Dynein has critical roles both in interphase and during cell division. Here, we focus on interphase cargoes of dynein, which include membrane-bound organelles, RNAs, protein complexes and viruses. A central challenge in the field is to understand how a single motor can transport such a diverse array of cargoes and how this process is regulated. The molecular basis by which each cargo is linked to dynein and its cofactor dynactin has started to emerge. Of particular importance for this process is a set of coiled-coil proteins — activating adaptors — that both recruit dynein–dynactin to their cargoes and activate dynein motility.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The dynein transport machinery.
Fig. 2: Many cargoes of dynein and their activating adaptors.
Fig. 3: Mechanisms linking dynein and dynactin to membrane cargoes.

Similar content being viewed by others

Change history

  • 08 May 2018

    In Figure 1c of the original article, ARP1 was incorrectly labelled as ARP11. The highlight for reference 37 was mistakenly placed under reference 36 and the highlight for reference 29 should have also referred to reference 16 (instead of 19). The HTML and PDF versions of the article have now been corrected.

References

  1. Gibbons, I. R. & Rowe, A. J. Dynein: a protein with adenosine triphosphatase activity from cilia. Science 149, 424–426 (1965). Describes the original discovery of dynein.

    Article  PubMed  CAS  Google Scholar 

  2. Paschal, B. M., Shpetner, H. S. & Vallee, R. B. MAP 1 C is a microtubule-activated ATPase which translocates microtubules in vitro and has dynein-like properties. J. Cell Biol. 105, 1273–1282 (1987). Describes the discovery of cytoplasmic dynein 1.

    Article  PubMed  CAS  Google Scholar 

  3. Paschal, B. M. & Vallee, R. B. Retrograde transport by the microtubule-associated protein MAP 1C. Nature 330, 181–183 (1987). Shows that cytoplasmic dynein 1 is a minus-end-directed motor.

    Article  PubMed  CAS  Google Scholar 

  4. Pazour, G. J., Dickert, B. L. & Witman, G. B. The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. J. Cell Biol. 144, 473–481 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Porter, M. E., Bower, R., Knott, J. A., Byrd, P. & Dentler, W. Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas. Mol. Biol. Cell 10, 693–712 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Gepner, J. et al. Cytoplasmic dynein function is essential in Drosophila melanogaster. Genetics 142, 865–878 (1996).

    PubMed  PubMed Central  CAS  Google Scholar 

  7. Harada, A. et al. Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein. J. Cell Biol. 141, 51–59 (1998). Characterization of dynein knockout mice, which shows that dynein is essential during development.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Lipka, J., Kuijpers, M., Jaworski, J. & Hoogenraad, C. C. Mutations in cytoplasmic dynein and its regulators cause malformations of cortical development and neurodegenerative diseases. Biochem. Soc. Trans. 41, 1605–1612 (2013).

    Article  PubMed  CAS  Google Scholar 

  9. Raaijmakers, J. A. & Medema, R. H. Function and regulation of dynein in mitotic chromosome segregation. Chromosoma 123, 407–422 (2014).

    Article  PubMed  CAS  Google Scholar 

  10. Gill, S. R. et al. Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein. J. Cell Biol. 115, 1639–1650 (1991).

    Article  PubMed  CAS  Google Scholar 

  11. Schroer, T. A. & Sheetz, M. P. Two activators of microtubule-based vesicle transport. J. Cell Biol. 115, 1309–1318 (1991). Along with reference 10, describes the discovery of dynactin.

    Article  PubMed  CAS  Google Scholar 

  12. Splinter, D. et al. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol. Biol. Cell 23, 4226–4241 (2012). Shows that the N-terminal domain of BICD2 strengthens the interaction between dynein and dynactin and activates motility in cells.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Mohler, J. & Wieschaus, E. F. Dominant maternal-effect mutations of Drosophila melanogaster causing the production of double-abdomen embryos. Genetics 112, 803–822 (1986).

    PubMed  PubMed Central  CAS  Google Scholar 

  14. McKenney, R. J., Huynh, W., Tanenbaum, M. E., Bhabha, G. & Vale, R. D. Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes. Science 345, 337–341 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Schlager, M. A., Hoang, H. T., Urnavicius, L., Bullock, S. L. & Carter, A. P. In vitro reconstitution of a highly processive recombinant human dynein complex. EMBO J. 33, 1855–1868 (2014). Along with reference 14, shows that coiled-coil containing activators like BICD2, along with dynactin, activate mammalian dynein to move processively.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Urnavicius, L. et al. Cryo-EM shows how dynactin recruits two dyneins for faster movement. Nature 554, 202–206 (2018).Describes the high-resolution structure of the dynein tail and shows that some activating adaptors preferentially recruit two dynein dimers.

    CAS  Google Scholar 

  17. Urnavicius, L. et al. The structure of the dynactin complex and its interaction with dynein. Science 347, 1441–1446 (2015). Reveals the structural basis for dynein activation by dynactin and the activating adaptor, BICD2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Zhang, K. et al. Cryo-EM reveals how human cytoplasmic dynein is auto-inhibited and activated. Cell 169, 1303–1314.e18 (2017). Demonstrates how dynactin activates the ability of dynein to move long distances.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Kon, T. et al. The 2.8 A crystal structure of the dynein motor domain. Nature 484, 345–350 (2012).

    Article  PubMed  CAS  Google Scholar 

  20. Schmidt, H., Gleave, E. S. & Carter, A. P. Insights into dynein motor domain function from a 3.3-A crystal structure. Nat. Struct. Mol. Biol. 19, 492–7, S1 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Schmidt, H., Zalyte, R., Urnavicius, L. & Carter, A. P. Structure of human cytoplasmic dynein-2 primed for its power stroke. Nature 518, 435–438 (2015).

    Article  PubMed  CAS  Google Scholar 

  22. Lee, I. G. et al. A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity. Nat. Commun. 9, 986 (2018).

  23. Schroeder, C. M., Ostrem, J. M., Hertz, N. T. & Vale, R. D. A. Ras-like domain in the light intermediate chain bridges the dynein motor to a cargo-binding region. eLife 3, e03351 (2014). Identifies the C-terminus of the DLIC as a binding site for activating adaptors.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Schroeder, C. M. & Vale, R. D. Assembly and activation of dynein-dynactin by the cargo adaptor protein Hook3. J. Cell Biol. 214, 309–318 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Carter, A. P., Diamant, A. G. & Urnavicius, L. How dynein and dynactin transport cargos: a structural perspective. Curr. Opin. Struct. Biol. 37, 62–70 (2016).

    Article  PubMed  CAS  Google Scholar 

  26. Waterman-Storer, C. M., Karki, S. & Holzbaur, E. L. The p150Glued component of the dynactin complex binds to both microtubules and the actin-related protein centractin (Arp-1). Proc. Natl Acad. Sci. USA 92, 1634–1638 (1995).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Gama, J. B. et al. Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly. J. Cell Biol. 216, 943–960 (2017). Identifies the CC1 box for DLIC binding in activating adaptors.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Horgan, C. P., Hanscom, S. R., Jolly, R. S., Futter, C. E. & McCaffrey, M. W. Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment. J. Cell Sci. 123, 181–191 (2010).

    Article  PubMed  CAS  Google Scholar 

  29. Grotjahn, D. A. et al. Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility. Nat. Struct. Mol. Biol. 25, 203–207 (2018). Along with reference 16, shows that dynactin can recruit two dynein dimers.

    Article  CAS  Google Scholar 

  30. Siglin, A. E. et al. Dynein and dynactin leverage their bivalent character to form a high-affinity interaction. PLoS ONE 8, e59453 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Kobayashi, T., Miyashita, T., Murayama, T. & Toyoshima, Y. Y. Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility. PLoS ONE 12, e0183672 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Torisawa, T. et al. Autoinhibition and cooperative activation mechanisms of cytoplasmic dynein. Nat. Cell Biol. 16, 1118–1124 (2014).

    Article  PubMed  CAS  Google Scholar 

  33. Cavalli, V., Kujala, P., Klumperman, J. & Goldstein, L. S. Sunday Driver links axonal transport to damage signaling. J. Cell Biol. 168, 775–787 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Jordens, I. et al. The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Curr. Biol. 11, 1680–1685 (2001).

    Article  PubMed  CAS  Google Scholar 

  35. Scherer, J., Yi, J. & Vallee, R. B. PKA-dependent dynein switching from lysosomes to adenovirus: a novel form of host-virus competition. J. Cell Biol. 205, 163–177 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Cianfrocco, M. A., DeSantis, M. E., Leschziner, A. E. & Reck-Peterson, S. L. Mechanism and regulation of cytoplasmic dynein. Annu. Rev. Cell Dev. Biol. 31, 83–108 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. DeSantis, M. E. et al. Lis1 has two opposing modes of regulating cytoplasmic dynein. Cell 170, 1197–1208.e12 (2017).Shows that LIS1 has two functionally distinct binding sites on the dynein motor domain.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Huang, J., Roberts, A. J., Leschziner, A. E. & Reck-Peterson, S. L. Lis1 acts as a “clutch” between the ATPase and microtubule-binding domains of the dynein motor. Cell 150, 975–986 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. McKenney, R. J., Weil, S. J., Scherer, J. & Vallee, R. B. Mutually exclusive cytoplasmic dynein regulation by NudE-Lis1 and dynactin. J. Biol. Chem. 286, 39615–39622 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Wang, S. & Zheng, Y. Identification of a novel dynein binding domain in nudel essential for spindle pole organization in Xenopus egg extract. J. Biol. Chem. 286, 587–593 (2011).

    Article  PubMed  CAS  Google Scholar 

  41. Zylkiewicz, E. et al. The N-terminal coiled-coil of Ndel1 is a regulated scaffold that recruits LIS1 to dynein. J. Cell Biol. 192, 433–445 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Torisawa, T. et al. Functional dissection of LIS1 and NDEL1 towards understanding the molecular mechanisms of cytoplasmic dynein regulation. J. Biol. Chem. 286, 1959–1965 (2011).

    Article  PubMed  CAS  Google Scholar 

  43. Yamada, M. et al. LIS1 and NDEL1 coordinate the plus-end-directed transport of cytoplasmic dynein. EMBO J. 27, 2471–2483 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Baumbach, J. et al. Lissencephaly-1 is a context-dependent regulator of the human dynein complex. eLife 6, e21768 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gutierrez, P. A., Ackermann, B. E., Vershinin, M. & McKenney, R. J. Differential effects of the dynein-regulatory factor Lissencephaly-1 on processive dynein-dynactin motility. J. Biol. Chem. 292, 12245–12255 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Wang, S. et al. Nudel/NudE and Lis1 promote dynein and dynactin interaction in the context of spindle morphogenesis. Mol. Biol. Cell 24, 3522–3533 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Seksek, O., Biwersi, J. & Verkman, A. S. Translational diffusion of macromolecule-sized solutes in cytoplasm and nucleus. J. Cell Biol. 138, 131–142 (1997).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Hutagalung, A. H. & Novick, P. J. Role of Rab GTPases in membrane traffic and cell physiology. Physiol. Rev. 91, 119–149 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Wozniak, M. J. et al. Role of kinesin-1 and cytoplasmic dynein in endoplasmic reticulum movement in VERO cells. J. Cell Sci. 122, 1979–1989 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Valenzuela, J. I. et al. Transport along the dendritic endoplasmic reticulum mediates the trafficking of GABAB receptors. J. Cell Sci. 127, 3382–3395 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Presley, J. F. et al. ER-to-Golgi transport visualized in living cells. Nature 389, 81–85 (1997). Elegantly demonstrates the role of dynein in transporting proteins from the ER to the Golgi apparatus.

    Article  PubMed  CAS  Google Scholar 

  52. Roghi, C. & Allan, V. J. Dynamic association of cytoplasmic dynein heavy chain 1a with the Golgi apparatus and intermediate compartment. J. Cell Sci. 112, 4673–4685 (1999).

    PubMed  CAS  Google Scholar 

  53. Salogiannis, J. & Reck-Peterson, S. L. Hitchhiking: a non-canonical mode of microtubule-based transport. Trends Cell Biol. 27, 141–150 (2017).

    Article  PubMed  CAS  Google Scholar 

  54. Guimaraes, S. C. et al. Peroxisomes, lipid droplets, and endoplasmic reticulum “hitchhike” on motile early endosomes. J. Cell Biol. 211, 945–954 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Wedlich-Soldner, R., Straube, A., Friedrich, M. W. & Steinberg, G. A balance of KIF1A-like kinesin and dynein organizes early endosomes in the fungus Ustilago maydis. EMBO J 21, 2946–2957 (2002).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Burkhardt, J. K., Echeverri, C. J., Nilsson, T. & Vallee, R. B. Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution. J. Cell Biol. 139, 469–484 (1997).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Hoogenraad, C. C. et al. Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes. EMBO J 20, 4041–4054 (2001). Demonstrates a link between BICD2 and dynein–dynactin.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Matanis, T. et al. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nat. Cell Biol. 4, 986–992 (2002).Shows that BICD proteins recruit dynein to RAB6-labelled Golgi vesicles.

    Article  PubMed  CAS  Google Scholar 

  59. Yadav, S., Puthenveedu, M. A. & Linstedt, A. D. Golgin160 recruits the dynein motor to position the Golgi apparatus. Dev. Cell 23, 153–165 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Schlager, M. A. et al. Bicaudal d family adaptor proteins control the velocity of Dynein-based movements. Cell Rep. 8, 1248–1256 (2014).

    Article  PubMed  CAS  Google Scholar 

  61. Schlager, M. A. et al. Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J. 29, 1637–1651 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Nokes, R. L., Fields, I. C., Collins, R. N. & Folsch, H. Rab13 regulates membrane trafficking between TGN and recycling endosomes in polarized epithelial cells. J. Cell Biol. 182, 845–853 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Bachmann-Gagescu, R. et al. The ciliopathy protein CC2D2A associates with NINL and functions in RAB8-MICAL3-regulated vesicle trafficking. PLoS Genet. 11, e1005575 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Baron Gaillard, C. L. et al. Hook2 is involved in the morphogenesis of the primary cilium. Mol. Biol. Cell 22, 4549–4562 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Driskell, O. J., Mironov, A., Allan, V. J. & Woodman, P. G. Dynein is required for receptor sorting and the morphogenesis of early endosomes. Nat. Cell Biol. 9, 113–120 (2007).

    Article  PubMed  CAS  Google Scholar 

  66. Heerssen, H. M., Pazyra, M. F. & Segal, R. A. Dynein motors transport activated Trks to promote survival of target-dependent neurons. Nat. Neurosci. 7, 596–604 (2004).

    Article  PubMed  CAS  Google Scholar 

  67. Kramer, H. & Phistry, M. Mutations in the Drosophila hook gene inhibit endocytosis of the boss transmembrane ligand into multivesicular bodies. J. Cell Biol. 133, 1205–1215 (1996).

    Article  PubMed  CAS  Google Scholar 

  68. Bielska, E. et al. Hook is an adapter that coordinates kinesin-3 and dynein cargo attachment on early endosomes. J. Cell Biol. 204, 989–1007 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Zhang, J. et al. HookA is a novel dynein-early endosome linker critical for cargo movement in vivo. J. Cell Biol. 204, 1009–1026 (2014). Along with reference 68, identifies a role for Hook proteins in dynein-based endosome motility.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Guo, X., Farias, G. G., Mattera, R. & Bonifacino, J. S. Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon. Proc. Natl Acad. Sci. USA 113, E5318–E5327 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Xu, L. et al. An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex. Mol. Biol. Cell 19, 5059–5071 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Yao, X., Wang, X. & Xiang, X. FHIP and FTS proteins are critical for dynein-mediated transport of early endosomes in Aspergillus. Mol. Biol. Cell 25, 2181–2189 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Gillingham, A. K., Sinka, R., Torres, I. L., Lilley, K. S. & Munro, S. Toward a comprehensive map of the effectors of rab GTPases. Dev. Cell 31, 358–373 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Gauthier, L. R. et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118, 127–138 (2004).

    Article  PubMed  CAS  Google Scholar 

  75. Caviston, J. P., Ross, J. L., Antony, S. M., Tokito, M. & Holzbaur, E. L. Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc. Natl Acad. Sci. USA 104, 10045–10050 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Engelender, S. et al. Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin. Hum. Mol. Genet. 6, 2205–2212 (1997).

    Article  PubMed  CAS  Google Scholar 

  77. Johansson, M. et al. Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin. J. Cell Biol. 176, 459–471 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Wu, M., Wang, T., Loh, E., Hong, W. & Song, H. Structural basis for recruitment of RILP by small GTPase Rab7. EMBO J. 24, 1491–1501 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Spang, A. Membrane tethering complexes in the endosomal system. Front. Cell Dev. Biol. 4, 35 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Lin, X. et al. RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking. Sci. Rep. 4, 7282 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. van der Kant, R. et al. Late endosomal transport and tethering are coupled processes controlled by RILP and the cholesterol sensor ORP1L. J. Cell Sci. 126, 3462–3474 (2013).

    Article  PubMed  CAS  Google Scholar 

  82. Szatmari, Z. et al. Rab11 facilitates cross-talk between autophagy and endosomal pathway through regulation of Hook localization. Mol. Biol. Cell 25, 522–531 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Pu, J., Guardia, C. M., Keren-Kaplan, T. & Bonifacino, J. S. Mechanisms and functions of lysosome positioning. J. Cell Sci. 129, 4329–4339 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Drerup, C. M. & Nechiporuk, A. V. JNK-interacting protein 3 mediates the retrograde transport of activated c-Jun N-terminal kinase and lysosomes. PLoS Genet. 9, e1003303 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Lorenzo, D. N. et al. A PIK3C3-ankyrin-B-dynactin pathway promotes axonal growth and multiorganelle transport. J. Cell Biol. 207, 735–752 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Cai, Q. et al. Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons. Neuron 68, 73–86 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Holleran, E. A., Tokito, M. K., Karki, S. & Holzbaur, E. L. Centractin (ARP1) associates with spectrin revealing a potential mechanism to link dynactin to intracellular organelles. J. Cell Biol. 135, 1815–1829 (1996).

    Article  PubMed  CAS  Google Scholar 

  88. Schmieg, N., Menendez, G., Schiavo, G. & Terenzio, M. Signalling endosomes in axonal transport: travel updates on the molecular highway. Semin. Cell Dev. Biol. 27, 32–43 (2014).

    Article  PubMed  CAS  Google Scholar 

  89. Delcroix, J. D. et al. NGF signaling in sensory neurons: evidence that early endosomes carry NGF retrograde signals. Neuron 39, 69–84 (2003).

    Article  PubMed  CAS  Google Scholar 

  90. Saxena, S., Bucci, C., Weis, J. & Kruttgen, A. The small GTPase Rab7 controls the endosomal trafficking and neuritogenic signaling of the nerve growth factor receptor TrkA. J. Neurosci. 25, 10930–10940 (2005).

    Article  PubMed  CAS  Google Scholar 

  91. Welz, T., Wellbourne-Wood, J. & Kerkhoff, E. Orchestration of cell surface proteins by Rab11. Trends Cell Biol. 24, 407–415 (2014).

    Article  PubMed  CAS  Google Scholar 

  92. Horgan, C. P. et al. Rab11-FIP3 is critical for the structural integrity of the endosomal recycling compartment. Traffic 8, 414–430 (2007).

    Article  PubMed  CAS  Google Scholar 

  93. Wang, J. & Deretic, D. The Arf and Rab11 effector FIP3 acts synergistically with ASAP1 to direct Rabin8 in ciliary receptor targeting. J. Cell Sci. 128, 1375–1385 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Wilson, G. M. et al. The FIP3-Rab11 protein complex regulates recycling endosome targeting to the cleavage furrow during late cytokinesis. Mol. Biol. Cell 16, 849–860 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Montagnac, G. et al. ARF6 Interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis. Curr. Biol. 19, 184–195 (2009).

    Article  PubMed  CAS  Google Scholar 

  96. Reilein, A. R. et al. Differential regulation of dynein-driven melanosome movement. Biochem. Biophys. Res. Commun. 309, 652–658 (2003).

    Article  PubMed  CAS  Google Scholar 

  97. Dona, M. et al. NINL and DZANK1 co-function in vesicle transport and are essential for photoreceptor development in zebrafish. PLoS Genet. 11, e1005574 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Redwine, W. B. et al. The human cytoplasmic dynein interactome reveals novel activators of motility. eLife 6, e28257 (2017). A proteomics resource of the cytoplasmic dynein interactome.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Kimura, S., Noda, T. & Yoshimori, T. Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes. Cell Struct. Funct. 33, 109–122 (2008).

    Article  PubMed  CAS  Google Scholar 

  100. Maday, S., Wallace, K. E. & Holzbaur, E. L. Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. J. Cell Biol. 196, 407–417 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Cheng, X. T., Zhou, B., Lin, M. Y., Cai, Q. & Sheng, Z. H. Axonal autophagosomes recruit dynein for retrograde transport through fusion with late endosomes. J. Cell Biol. 209, 377–386 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Lee, S., Sato, Y. & Nixon, R. A. Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer’s-like axonal dystrophy. J. Neurosci. 31, 7817–7830 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Maday, S. & Holzbaur, E. L. Compartment-specific regulation of autophagy in primary neurons. J. Neurosci. 36, 5933–5945 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Ravikumar, B. et al. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat. Genet. 37, 771–776 (2005).

    Article  PubMed  CAS  Google Scholar 

  105. Wong, Y. C. & Holzbaur, E. L. The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation. J. Neurosci. 34, 1293–1305 (2014). Demonstrates the roles of HTT and HAP1 in autophagy.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Fu, M. M., Nirschl, J. J. & Holzbaur, E. L. LC3 binding to the scaffolding protein JIP1 regulates processive dynein-driven transport of autophagosomes. Dev. Cell 29, 577–590 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Klinman, E. & Holzbaur, E. L. Comparative analysis of axonal transport markers in primary mammalian neurons. Methods Cell Biol. 131, 409–424 (2016). Shows different types of retrograde transport of many key cargoes in axons.

    Article  PubMed  Google Scholar 

  108. Hollenbeck, P. J. & Saxton, W. M. The axonal transport of mitochondria. J. Cell Sci. 118, 5411–5419 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Pilling, A. D., Horiuchi, D., Lively, C. M. & Saxton, W. M. Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons. Mol. Biol. Cell 17, 2057–2068 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Schwarz, T. L. Mitochondrial trafficking in neurons. Cold Spring Harb. Perspect. Biol. 5, a011304 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. van Spronsen, M. et al. TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites. Neuron 77, 485–502 (2013).

    Article  PubMed  CAS  Google Scholar 

  112. Neuhaus, A., Eggeling, C., Erdmann, R. & Schliebs, W. Why do peroxisomes associate with the cytoskeleton? Biochim. Biophys. Acta 1863, 1019–1026 (2016).

    Article  PubMed  CAS  Google Scholar 

  113. Schrader, M., King, S. J., Stroh, T. A. & Schroer, T. A. Real time imaging reveals a peroxisomal reticulum in living cells. J. Cell Sci. 113, 3663–3671 (2000).

    PubMed  CAS  Google Scholar 

  114. Okumoto, K. et al.New splicing variants of mitochondrial Rho GTPase-1 (Miro) transport peroxisomes. J. Cell Biol. 217, 619–633 (2017).

    Google Scholar 

  115. Egan, M. J., Tan, K. & Reck-Peterson, S. L. Lis1 is an initiation factor for dynein-driven organelle transport. J. Cell Biol. 197, 971–982 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Salogiannis, J., Egan, M. J. & Reck-Peterson, S. L. Peroxisomes move by hitchhiking on early endosomes using the novel linker protein PxdA. J. Cell Biol. 212, 289–296 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Thiam, A. R., Farese, R. V. Jr & Walther, T. C. The biophysics and cell biology of lipid droplets. Nat. Rev. Mol. Cell Biol. 14, 775–786 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Targett-Adams, P. et al. Live cell analysis and targeting of the lipid droplet-binding adipocyte differentiation-related protein. J. Biol. Chem. 278, 15998–16007 (2003).

    Article  PubMed  CAS  Google Scholar 

  119. Gross, S. P., Welte, M. A., Block, S. M. & Wieschaus, E. F. Dynein-mediated cargo transport in vivo. A switch controls travel distance. J. Cell Biol. 148, 945–956 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Shubeita, G. T. et al. Consequences of motor copy number on the intracellular transport of kinesin-1-driven lipid droplets. Cell 135, 1098–1107 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Larsen, K. S., Xu, J., Cermelli, S., Shu, Z. & Gross, S. P. BicaudalD actively regulates microtubule motor activity in lipid droplet transport. PLoS ONE 3, e3763 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. McNally, F. J. Mechanisms of spindle positioning. J. Cell Biol. 200, 131–140 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Moore, J. K., Stuchell-Brereton, M. D. & Cooper, J. A. Function of dynein in budding yeast: mitotic spindle positioning in a polarized cell. Cell. Motil. Cytoskeleton 66, 546–555 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Plamann, M., Minke, P. F., Tinsley, J. H. & Bruno, K. S. Cytoplasmic dynein and actin-related protein Arp1 are required for normal nuclear distribution in filamentous fungi. J. Cell Biol. 127, 139–149 (1994).

    Article  PubMed  CAS  Google Scholar 

  125. Xiang, X., Beckwith, S. M. & Morris, N. R. Cytoplasmic dynein is involved in nuclear migration in Aspergillus nidulans. Proc. Natl Acad. Sci. USA 91, 2100–2104 (1994).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Gonczy, P., Pichler, S., Kirkham, M. & Hyman, A. A. Cytoplasmic dynein is required for distinct aspects of MTOC positioning, including centrosome separation, in the one cell stage Caenorhabditis elegans embryo. J. Cell Biol. 147, 135–150 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Dujardin, D. L. et al. A role for cytoplasmic dynein and LIS1 in directed cell movement. J. Cell Biol. 163, 1205–1211 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Tsai, J. W., Bremner, K. H. & Vallee, R. B. Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nat. Neurosci. 10, 970–979 (2007).

    Article  PubMed  CAS  Google Scholar 

  129. Tsai, J. W., Lian, W. N., Kemal, S., Kriegstein, A. R. & Vallee, R. B. Kinesin 3 and cytoplasmic dynein mediate interkinetic nuclear migration in neural stem cells. Nat. Neurosci. 13, 1463–1471 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Cadot, B., Gache, V. & Gomes, E. R. Moving and positioning the nucleus in skeletal muscle — one step at a time. Nucleus 6, 373–381 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Folker, E. S., Schulman, V. K. & Baylies, M. K. Translocating myonuclei have distinct leading and lagging edges that require kinesin and dynein. Development 141, 355–366 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Radulescu, A. E. & Cleveland, D. W. NuMA after 30 years: the matrix revisited. Trends Cell Biol. 20, 214–222 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Hu, D. J. et al. Dynein recruitment to nuclear pores activates apical nuclear migration and mitotic entry in brain progenitor cells. Cell 154, 1300–1313 (2013).

    Article  PubMed  CAS  Google Scholar 

  134. Splinter, D. et al. Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry. PLoS Biol. 8, e1000350 (2010). Demonstrates a role for BICD2 in dynein recruitment to nuclear pores.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Bolhy, S. et al. A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase. J. Cell Biol. 192, 855–871 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Malone, C. J. et al. The C. elegans hook protein, ZYG-12, mediates the essential attachment between the centrosome and nucleus. Cell 115, 825–836 (2003).

    Article  PubMed  CAS  Google Scholar 

  137. Bullock, S. L. Messengers, motors and mysteries: sorting of eukaryotic mRNAs by cytoskeletal transport. Biochem. Soc. Trans. 39, 1161–1165 (2011).

    Article  PubMed  CAS  Google Scholar 

  138. Bullock, S. L. & Ish-Horowicz, D. Conserved signals and machinery for RNA transport in Drosophila oogenesis and embryogenesis. Nature 414, 611–616 (2001). Demonstrates a role for BicD in RNA localization.

    Article  PubMed  CAS  Google Scholar 

  139. Wilkie, G. S. & Davis, I. Drosophila wingless and pair-rule transcripts localize apically by dynein-mediated transport of RNA particles. Cell 105, 209–219 (2001).

    Article  PubMed  CAS  Google Scholar 

  140. Gershoni-Emek, N. et al. Proteomic analysis of dynein-interacting proteins in amyotrophic lateral sclerosis synaptosomes reveals alterations in the RNA-binding protein Staufen1. Mol. Cell Proteom. 15, 506–522 (2016).

    Article  CAS  Google Scholar 

  141. van Niekerk, E. A. et al. Sumoylation in axons triggers retrograde transport of the RNA-binding protein La. Proc. Natl Acad. Sci. USA 104, 12913–12918 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Dienstbier, M., Boehl, F., Li, X. & Bullock, S. L. Egalitarian is a selective RNA-binding protein linking mRNA localization signals to the dynein motor. Genes Dev. 23, 1546–1558 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Weil, T. T. mRNA localization in the Drosophila germline. RNA Biol. 11, 1010–1018 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Clark, A., Meignin, C. & Davis, I. A. Dynein-dependent shortcut rapidly delivers axis determination transcripts into the Drosophila oocyte. Development 134, 1955–1965 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Mische, S., Li, M., Serr, M. & Hays, T. S. Direct observation of regulated ribonucleoprotein transport across the nurse cell/oocyte boundary. Mol. Biol. Cell 18, 2254–2263 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Weil, T. T., Forrest, K. M. & Gavis, E. R. Localization of bicoid mRNA in late oocytes is maintained by continual active transport. Dev. Cell 11, 251–262 (2006).

    Article  PubMed  CAS  Google Scholar 

  147. Bianco, A., Dienstbier, M., Salter, H. K., Gatto, G. & Bullock, S. L. Bicaudal-D regulates fragile X mental retardation protein levels, motility, and function during neuronal morphogenesis. Curr. Biol. 20, 1487–1492 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  148. Haag, C., Steuten, B. & Feldbrugge, M. Membrane-coupled mRNA trafficking in fungi. Annu. Rev. Microbiol. 69, 265–281 (2015).

    Article  PubMed  CAS  Google Scholar 

  149. Baumann, S., Konig, J., Koepke, J. & Feldbrugge, M. Endosomal transport of septin mRNA and protein indicates local translation on endosomes and is required for correct septin filamentation. EMBO Rep. 15, 94–102 (2014).

    Article  PubMed  CAS  Google Scholar 

  150. Higuchi, Y., Ashwin, P., Roger, Y. & Steinberg, G. Early endosome motility spatially organizes polysome distribution. J. Cell Biol. 204, 343–357 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Garcia-Mata, R., Gao, Y. S. & Sztul, E. Hassles with taking out the garbage: aggravating aggresomes. Traffic 3, 388–396 (2002).

    Article  PubMed  CAS  Google Scholar 

  152. Garcia-Mata, R., Bebok, Z., Sorscher, E. J. & Sztul, E. S. Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. J. Cell Biol. 146, 1239–1254 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Johnston, J. A., Illing, M. E. & Kopito, R. R. Cytoplasmic dynein/dynactin mediates the assembly of aggresomes. Cell. Motil. Cytoskeleton 53, 26–38 (2002).

    Article  PubMed  CAS  Google Scholar 

  154. Kawaguchi, Y. et al. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115, 727–738 (2003).

    Article  PubMed  CAS  Google Scholar 

  155. Yan, J. et al. SQSTM1/p62 interacts with HDAC6 and regulates deacetylase activity. PLoS ONE 8, e76016 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  156. Calderilla-Barbosa, L. et al. Interaction of SQSTM1 with the motor protein dynein — SQSTM1 is required for normal dynein function and trafficking. J. Cell Sci. 127, 4052–4063 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Gamerdinger, M., Kaya, A. M., Wolfrum, U., Clement, A. M. & Behl, C. BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep. 12, 149–156 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Xu, Z. et al. 14-3-3 protein targets misfolded chaperone-associated proteins to aggresomes. J. Cell Sci. 126, 4173–4186 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Perry, R. B. & Fainzilber, M. Local translation in neuronal processes — in vivo tests of a “heretical hypothesis”. Dev. Neurobiol. 74, 210–217 (2014).

    Article  PubMed  CAS  Google Scholar 

  160. Ben-Yaakov, K. et al. Axonal transcription factors signal retrogradely in lesioned peripheral nerve. EMBO J. 31, 1350–1363 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Hanz, S. et al. Axoplasmic importins enable retrograde injury signaling in lesioned nerve. Neuron 40, 1095–1104 (2003).

    Article  PubMed  CAS  Google Scholar 

  162. Lowery, J., Kuczmarski, E. R., Herrmann, H. & Goldman, R. D. Intermediate filaments play a pivotal role in regulating cell architecture and function. J. Biol. Chem. 290, 17145–17153 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Hookway, C. et al. Microtubule-dependent transport and dynamics of vimentin intermediate filaments. Mol. Biol. Cell 26, 1675–1686 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Helfand, B. T., Mikami, A., Vallee, R. B. & Goldman, R. D. A requirement for cytoplasmic dynein and dynactin in intermediate filament network assembly and organization. J. Cell Biol. 157, 795–806 (2002).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Payne, C., Rawe, V., Ramalho-Santos, J., Simerly, C. & Schatten, G. Preferentially localized dynein and perinuclear dynactin associate with nuclear pore complex proteins to mediate genomic union during mammalian fertilization. J. Cell Sci. 116, 4727–4738 (2003).

    Article  PubMed  CAS  Google Scholar 

  166. He, Y. et al. Role of cytoplasmic dynein in the axonal transport of microtubules and neurofilaments. J. Cell Biol. 168, 697–703 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Wagner, O. I. et al. The interaction of neurofilaments with the microtubule motor cytoplasmic dynein. Mol. Biol. Cell 15, 5092–5100 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  168. Ahmad, F. J., Echeverri, C. J., Vallee, R. B. & Baas, P. W. Cytoplasmic dynein and dynactin are required for the transport of microtubules into the axon. J. Cell Biol. 140, 391–401 (1998).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. del Castillo, U., Winding, M., Lu, W. & Gelfand, V. I. Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons. eLife 4, e10140 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  170. Tang, N. & Marshall, W. F. Centrosome positioning in vertebrate development. J. Cell Sci. 125, 4951–4961 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  171. Jia, Y., Fong, K. W., Choi, Y. K., See, S. S. & Qi, R. Z. Dynamic recruitment of CDK5RAP2 to centrosomes requires its association with dynein. PLoS ONE 8, e68523 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Fong, K. W., Choi, Y. K., Rattner, J. B. & Qi, R. Z. CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the gamma-tubulin ring complex. Mol. Biol. Cell 19, 115–125 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. Casenghi, M. et al. Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation. Dev. Cell 5, 113–125 (2003).

    Article  PubMed  CAS  Google Scholar 

  174. Mogensen, M. M., Malik, A., Piel, M., Bouckson-Castaing, V. & Bornens, M. Microtubule minus-end anchorage at centrosomal and non-centrosomal sites: the role of ninein. J. Cell Sci. 113, 3013–3023 (2000).

    PubMed  CAS  Google Scholar 

  175. Szebenyi, G., Hall, B., Yu, R., Hashim, A. I. & Kramer, H. Hook2 localizes to the centrosome, binds directly to centriolin/CEP110 and contributes to centrosomal function. Traffic 8, 32–46 (2007).

    Article  PubMed  CAS  Google Scholar 

  176. Hori, A. & Toda, T. Regulation of centriolar satellite integrity and its physiology. Cell. Mol. Life Sci. 74, 213–229 (2017).

    Article  PubMed  CAS  Google Scholar 

  177. Kim, J. C. et al. The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nat. Genet. 36, 462–470 (2004).

    Article  PubMed  CAS  Google Scholar 

  178. Dammermann, A. & Merdes, A. Assembly of centrosomal proteins and microtubule organization depends on PCM-1. J. Cell Biol. 159, 255–266 (2002).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Ge, X., Frank, C. L., Calderon de Anda, F. & Tsai, L. H. Hook3 interacts with PCM1 to regulate pericentriolar material assembly and the timing of neurogenesis. Neuron 65, 191–203 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Cao, J. et al. Circovirus transport proceeds via direct interaction of the cytoplasmic dynein IC1 subunit with the viral capsid protein. J. Virol. 89, 2777–2791 (2015).

    Article  PubMed  CAS  Google Scholar 

  181. Castle, M. J., Perlson, E., Holzbaur, E. L. & Wolfe, J. H. Long-distance axonal transport of AAV9 is driven by dynein and kinesin-2 and is trafficked in a highly motile Rab7-positive compartment. Mol. Ther. 22, 554–566 (2014).

    Article  PubMed  CAS  Google Scholar 

  182. Dodding, M. P. & Way, M. Coupling viruses to dynein and kinesin-1. EMBO J 30, 3527–3539 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  183. Lakadamyali, M., Rust, M. J., Babcock, H. P. & Zhuang, X. Visualizing infection of individual influenza viruses. Proc. Natl Acad. Sci. USA 100, 9280–9285 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  184. Petit, C. et al. Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8. J. Cell Sci. 116, 3433–3442 (2003).

    Article  PubMed  CAS  Google Scholar 

  185. Alonso, C. et al. African swine fever virus protein p54 interacts with the microtubular motor complex through direct binding to light-chain dynein. J. Virol. 75, 9819–9827 (2001).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  186. Mainou, B. A. et al. Reovirus cell entry requires functional microtubules. mBio 4, e00405–13 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  187. Ploubidou, A. et al. Vaccinia virus infection disrupts microtubule organization and centrosome function. EMBO J. 19, 3932–3944 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  188. Ramanathan, H. N. et al. Dynein-dependent transport of the hantaan virus nucleocapsid protein to the endoplasmic reticulum-Golgi intermediate compartment. J. Virol. 81, 8634–8647 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  189. Shrivastava, N., Sripada, S., Kaur, J., Shah, P. S. & Cecilia, D. Insights into the internalization and retrograde trafficking of Dengue 2 virus in BHK-21 cells. PLoS ONE 6, e25229 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  190. Klingen, Y., Conzelmann, K. K. & Finke, S. Double-labeled rabies virus: live tracking of enveloped virus transport. J. Virol. 82, 237–245 (2008).

    Article  PubMed  CAS  Google Scholar 

  191. Boulant, S. et al. Hepatitis C virus core protein induces lipid droplet redistribution in a microtubule- and dynein-dependent manner. Traffic 9, 1268–1282 (2008).

    Article  PubMed  CAS  Google Scholar 

  192. Kim, S. et al. Hepatitis B virus x protein induces perinuclear mitochondrial clustering in microtubule- and Dynein-dependent manners. J. Virol. 81, 1714–1726 (2007).

    Article  PubMed  CAS  Google Scholar 

  193. Banerjee, I. et al. Influenza A virus uses the aggresome processing machinery for host cell entry. Science 346, 473–477 (2014).

    Article  PubMed  CAS  Google Scholar 

  194. Lycke, E. et al. Herpes simplex virus infection of the human sensory neuron. An electron microscopy study. Arch. Virol. 101, 87–104 (1988).

    Article  PubMed  CAS  Google Scholar 

  195. Radtke, K. et al. Plus- and minus-end directed microtubule motors bind simultaneously to herpes simplex virus capsids using different inner tegument structures. PLoS Pathog. 6, e1000991 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  196. Zaichick, S. V. et al. The herpesvirus VP1/2 protein is an effector of dynein-mediated capsid transport and neuroinvasion. Cell Host Microbe 13, 193–203 (2013). Provides evidence that a herpes virus contains a protein that can activate dynein–dynactin transport.

    Article  PubMed  CAS  Google Scholar 

  197. Suomalainen, M. et al. Microtubule-dependent plus- and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J. Cell Biol. 144, 657–672 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  198. Bremner, K. H. et al. Adenovirus transport via direct interaction of cytoplasmic dynein with the viral capsid hexon subunit. Cell Host Microbe 6, 523–535 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  199. Suikkanen, S. et al. Exploitation of microtubule cytoskeleton and dynein during parvoviral traffic toward the nucleus. J. Virol. 77, 10270–10279 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  200. Mazarakis, N. D. et al. Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde axonal transport and access to the nervous system after peripheral delivery. Hum. Mol. Genet. 10, 2109–2121 (2001).

    Article  PubMed  CAS  Google Scholar 

  201. Laan, L. et al. Cortical dynein controls microtubule dynamics to generate pulling forces that position microtubule asters. Cell 148, 502–514 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Ligon, L. A., Karki, S., Tokito, M. & Holzbaur, E. L. Dynein binds to beta-catenin and may tether microtubules at adherens junctions. Nat. Cell Biol. 3, 913–917 (2001).

    Article  PubMed  CAS  Google Scholar 

  203. Rosse, C. et al. Binding of dynein intermediate chain 2 to paxillin controls focal adhesion dynamics and migration. J. Cell Sci. 125, 3733–3738 (2012).

    Article  PubMed  CAS  Google Scholar 

  204. Mallik, R., Rai, A. K., Barak, P., Rai, A. & Kunwar, A. Teamwork in microtubule motors. Trends Cell Biol. 23, 575–582 (2013).

    Article  PubMed  CAS  Google Scholar 

  205. Hancock, W. O. Bidirectional cargo transport: moving beyond tug of war. Nat. Rev. Mol. Cell Biol. 15, 615–628 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Grigoriev, I. et al. Rab6 regulates transport and targeting of exocytotic carriers. Dev. Cell 13, 305–314 (2007).

    Article  PubMed  CAS  Google Scholar 

  207. Block-Galarza, J. et al. Fast transport and retrograde movement of huntingtin and HAP 1 in axons. Neuroreport 8, 2247–2251 (1997).

    Article  PubMed  CAS  Google Scholar 

  208. Li, S. H., Gutekunst, C. A., Hersch, S. M. & Li, X. J. Interaction of huntingtin-associated protein with dynactin P150Glued. J. Neurosci. 18, 1261–1269 (1998).

    Article  PubMed  CAS  Google Scholar 

  209. Fu, M. M. & Holzbaur, E. L. JIP1 regulates the directionality of APP axonal transport by coordinating kinesin and dynein motors. J. Cell Biol. 202, 495–508 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  210. Hong, Z. et al. The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport. Cell Res. 19, 1334–1349 (2009).

    Article  PubMed  CAS  Google Scholar 

  211. Wassmer, T. et al. The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network. Dev. Cell 17, 110–122 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  212. Holleran, E. A. et al. βIII spectrin binds to the Arp1 subunit of dynactin. J. Biol. Chem. 276, 36598–36605 (2001).

    Article  PubMed  CAS  Google Scholar 

  213. Starcevic, M. & Dell’Angelica, E. C. Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1). J. Biol. Chem. 279, 28393–28401 (2004).

    Article  PubMed  CAS  Google Scholar 

  214. Tynan, S. H., Purohit, A., Doxsey, S. J. & Vallee, R. B. Light intermediate chain 1 defines a functional subfraction of cytoplasmic dynein which binds to pericentrin. J. Biol. Chem. 275, 32763–32768 (2000).

    Article  PubMed  CAS  Google Scholar 

  215. Schmoranzer, J. et al. Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration. Curr. Biol. 19, 1065–1074 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  216. Williams, J. C. et al. Structural and thermodynamic characterization of a cytoplasmic dynein light chain-intermediate chain complex. Proc. Natl Acad. Sci. USA 104, 10028–10033 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  217. Tai, A. W., Chuang, J. Z., Bode, C., Wolfrum, U. & Sung, C. H. Rhodopsin’s carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1. Cell 97, 877–887 (1999).

    Article  PubMed  CAS  Google Scholar 

  218. Tai, A. W., Chuang, J. Z. & Sung, C. H. Cytoplasmic dynein regulation by subunit heterogeneity and its role in apical transport. J. Cell Biol. 153, 1499–1509 (2001).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  219. Meiri, D. et al. Mechanistic insight into the microtubule and actin cytoskeleton coupling through dynein-dependent RhoGEF inhibition. Mol. Cell 45, 642–655 (2012).

    Article  PubMed  CAS  Google Scholar 

  220. Wu, H., Maciejewski, M. W., Takebe, S. & King, S. M. Solution structure of the Tctex1 dimer reveals a mechanism for dynein-cargo interactions. Structure 13, 213–223 (2005).

    Article  PubMed  CAS  Google Scholar 

  221. Echeverri, C. J., Paschal, B. M., Vaughan, K. T. & Vallee, R. B. Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis. J. Cell Biol. 132, 617–633 (1996). Presents the discovery that p50 overexpression inhibits dynein function.

    Article  PubMed  CAS  Google Scholar 

  222. Quintyne, N. J. et al. Dynactin is required for microtubule anchoring at centrosomes. J. Cell Biol. 147, 321–334 (1999). Presents the discovery that overexpression of the CC1 fragment of the p150 dynactin subunit inhibits dynein function.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  223. Schroer, T. A. Dynactin. Annu. Rev. Cell Dev. Biol. 20, 759–779 (2004).

    Article  PubMed  CAS  Google Scholar 

  224. Steffen, W. et al. The involvement of the intermediate chain of cytoplasmic dynein in binding the motor complex to membranous organelles of Xenopus oocytes. Mol. Biol. Cell 8, 2077–2088 (1997).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  225. Hoogenraad, C. C. et al. Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. EMBO J. 22, 6004–6015 (2003). The first use of a relocation assay to monitor dynein recruitment and activation.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  226. Kapitein, L. C. et al. Probing intracellular motor protein activity using an inducible cargo trafficking assay. Biophys. J. 99, 2143–2152 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  227. Olenick, M. A., Tokito, M., Boczkowska, M., Dominguez, R. & Holzbaur, E. L. Hook adaptors induce unidirectional processive motility by enhancing the dynein-dynactin interaction. J. Biol. Chem. 291, 18239–18251 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  228. Griffis, E. R., Stuurman, N. & Vale, R. D. Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J. Cell Biol. 177, 1005–1015 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  229. Maldonado-Baez, L., Cole, N. B., Kramer, H. & Donaldson, J. G. Microtubule-dependent endosomal sorting of clathrin-independent cargo by Hook1. J. Cell Biol. 201, 233–247 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  230. Walenta, J. H., Didier, A. J., Liu, X. & Kramer, H. The Golgi-associated hook3 protein is a member of a novel family of microtubule-binding proteins. J. Cell Biol. 152, 923–934 (2001). Describes the discovery of the Hook family of proteins.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  231. Fumoto, K., Hoogenraad, C. C. & Kikuchi, A. GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome. EMBO J. 25, 5670–5682 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  232. Okuda, H. et al. LRGUK1 is part of a multiprotein complex required for manchette function and male fertility. FASEB J. 31, 1141–1152 (2017).

    Article  PubMed  CAS  Google Scholar 

  233. Ham, H., Huynh, W., Schoon, R. A., Vale, R. D. & Billadeau, D. D. HkRP3 is a microtubule-binding protein regulating lytic granule clustering and NK cell killing. J. Immunol. 194, 3984–3996 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  234. Merdes, A., Heald, R., Samejima, K., Earnshaw, W. C. & Cleveland, D. W. Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J. Cell Biol. 149, 851–862 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  235. Hueschen, C., Kenny, S. J., Xu, K. & Dumont, S. NuMA targets dynein to microtubule minus-ends at mitosis. bioRxiv https://doi.org/10.1101/148692 (2017).

  236. Dohner, K. et al. Function of dynein and dynactin in herpes simplex virus capsid transport. Mol. Biol. Cell 13, 2795–2809 (2002).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  237. Smith, G. A., Pomeranz, L., Gross, S. P. & Enquist, L. W. Local modulation of plus-end transport targets herpesvirus entry and egress in sensory axons. Proc. Natl Acad. Sci. USA 101, 16034–16039 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  238. Zila, V., Difato, F., Klimova, L., Huerfano, S. & Forstova, J. Involvement of microtubular network and its motors in productive endocytic trafficking of mouse polyomavirus. PLoS ONE 9, e96922 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  239. Liu, W. J. et al. Association of bovine papillomavirus type 1 with microtubules. Virology 282, 237–244 (2001).

    Article  PubMed  CAS  Google Scholar 

  240. Eyre, N. S. et al. Dynamic imaging of the hepatitis C virus NS5A protein during a productive infection. J. Virol. 88, 3636–3652 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  241. Sfakianos, J. N., LaCasse, R. A. & Hunter, E. The M-PMV cytoplasmic targeting-retention signal directs nascent Gag polypeptides to a pericentriolar region of the cell. Traffic 4, 660–670 (2003).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank M. DeSantis, J. Salogiannis and J. Srouji for critical comments on the manuscript. S.L.R.-P. is a Howard Hughes Medical Institute-Simons Faculty Scholar and is funded by National Institutes of Health (NIH) grants R01GM107214 and R01GM121772. A.P.C. is funded by the Wellcome Trust (WT100387) and the Medical Research Council, UK (MC_UP_A025_1011). R.D.V. is a Howard Hughes Medical Institute investigator and funded by NIH grant R01 GM097312. The authors apologize to their colleagues whose work they did not have space to cite. We dedicate this review to the memory of Ian Gibbons, discoverer of dynein, who passed away earlier this year.

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA

    Samara L. Reck-Peterson & William B. Redwine

  2. Division of Biological Sciences, Cell and Developmental Biology Section, University of California San Diego, La Jolla, CA, USA

    Samara L. Reck-Peterson

  3. Department of Cell Biology, Harvard Medical School, Boston, MA, USA

    William B. Redwine

  4. Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA

    Ronald D. Vale

  5. MRC Laboratory of Molecular Biology, Cambridge, UK

    Andrew P. Carter

Authors
  1. Samara L. Reck-Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William B. Redwine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ronald D. Vale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew P. Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.L.R.-P., A.P.C. and W.B.R. researched data for the article. S.L.R.-P., A.P.C. and R.D.V. discussed the content of the article, S.L.R.-P., A.P.C., W.B.R. and R.D.V. wrote and edited the article.

Corresponding authors

Correspondence to Samara L. Reck-Peterson or Andrew P. Carter.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Lissencephaly

Derived from Greek for ‘smooth brain’; a spectrum of developmental disorders characterized by defective neuronal migration and the resulting lack of brain folds and grooves.

AAA+ domains

Domains that are a highly conserved ATPase fold.

WD40 domain

A structural domain formed from WD40 repeats, themselves composed of approximately 40 amino acids and often ending in tryptophan (W), followed by aspartic acid (D).

SNARE

Proteins that are anchored to either donor or acceptor membranes, mediating fusion between distinct membranes.

BLOC-1

A multisubunit protein complex that contributes to membrane tubulation, which is important for sorting and organelle biogenesis in the endolysosomal system.

RAS-like domain

A protein domain with sequence similarity to the GTPase domain of RAS.

Barbed end

The end where myosin can be seen protruding when actin filaments are decorated with myosin motor domains and visualized by electron microscopy; similar nomenclature is used to refer to the equivalent end of the α-centractin (ARP1) minifilament in dynactin.

Pointed end

The end where myosin cannot be seen protruding when actin filaments are decorated with myosin motor domains and visualized by electron microscopy; similar nomenclature is used to refer to the equivalent end of the α-centractin (ARP1) minifilament in dynactin.

EF hands

A helix–loop–helix protein structural domain that often confers a protein with calcium-binding ability.

β-propellers

A protein structural domain characterized by four to eight wedge-shaped β-sheets arranged similarly to the blades on a propeller.

Cell cortex

The cytoplasmic face of the plasma membrane.

Total internal reflection microscopy

A microscopy technique that results in illumination of only a region approximately 100 nm from the coverslip surface, allowing high signal-to-noise ratios to be achieved, which makes it feasible to image and track single molecules.

Recycling endosomes

Endocytic vesicles characterized by the presence of the RAS-related protein RAB11 that direct the anterograde trafficking of materials to the cell surface.

Late endosomes

Pre-lysosomal endocytic vesicles with lower internal pH relative to early endosomes and characterized by the presence of the protein RAS-related protein RAB7a (RAB7).

Multivesicular bodies

(MVBs). Late endosomes that contain multiple internalized vesicles.

HOPS complex

A multisubunit membrane-tethering complex that participates in organelle fusion events within the endolysosomal system in concert with RAB proteins.

Pronuclei

The distinct egg and sperm nuclei that are present within a single cell at the onset of fertilization before the fusion of their genetic material.

Interkinetic nuclear migration

The cell cycle-dependent movement of nuclei observed in neural progenitor cells.

Syncytial blastoderm

Tissue that builds early Drosophila melanogaster embryo and that is characterized by multiple nuclei residing in a shared cytoplasm, which is the result of multiple nuclear divisions in the absence of cytokinesis.

Nurse cells

A group of 15 polyploid Drosophila melanogaster ovarian cells that share a cytoplasm with each other and the developing oocyte and function to support the development of the oocyte by providing nutrients and biomolecules (mRNAs and proteins) through intercellular connections called ring canals.

Dendritic branching

The process by which a dendrite, the portion of neuron that receives signals from other cells, forms the cellular projections it contributes to synapses.

Polysomes

The complex formed by two or more ribosomes simultaneously engaged in translation along the length of a single messenger RNA.

14-3-3 protein

A conserved family of adaptor proteins that interact with diverse proteins and regulate their function through, for example, altered localization, activity or stability.

Importins

Proteins that recognize and deliver proteins with nuclear localization signals into the nucleus through nuclear pores.

γ-tubulin

Tubulin family member that, as a component of γ-tubulin ring complexes, templates nascent microtubules.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reck-Peterson, S.L., Redwine, W.B., Vale, R.D. et al. The cytoplasmic dynein transport machinery and its many cargoes. Nat Rev Mol Cell Biol 19, 382–398 (2018). https://doi.org/10.1038/s41580-018-0004-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41580-018-0004-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing