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Regulators of the cytoplasmic dynein motor

Nature Reviews Molecular Cell Biology volume 10, pages 854–865 (2009)Cite this article

Key Points

  • Cytoplasmic dynein is the only microtubule minus end-directed motor in the cytoplasm of most eukaryotic cells and therefore carries out a huge range of functions, including organelle and mRNA transport, nuclear and spindle positioning, and transport of the mitotic spindle assembly checkpoint proteins.

  • The dynein motor functions as a holoenzyme, assembling into a complex with several smaller, non-catalytic subunits that help to connect it with dynein cargos as well as other regulatory factors that help to couple the dynein motor to its many cellular functions.

  • Two dynein adaptors, dynactin and a complex of lissencephaly 1 (Lis1) and nuclear distribution protein E (NUDE) or NUDE-like (NUDEL) seem to be ubiquitously required for all dynein functions. Dynactin increases dynein processivity in vitro and helps to link dynein with its cargos and anchor points in the cell. LIS1–NUDE and LIS1–NUDEL might act primarily as a switch for dynein activity. Both dynactin and LIS1–NUDE and LIS1–NUDELmodulate dynein association with the plus ends of microtubules, which seems to be important for the delivery of dynein to its sites of activity.

  • Bicaudal D and the Rod–ZW10–Zwilch (RZZ) complex are multifunctional dynein adaptors, but are restricted to metazoan organisms. Bicaudal D links dynein with several interphase cargos, and RZZ, with its partner Spindly, docks dynein at the mitotic kinetochore and might help to regulate the transition between the several dynein functions at the kinetochore.

  • Small GTPases, which are highly specific to subcellular compartments, regulate dynein association with some of its cargos.

  • Dynein's adaptors are heavily interconnected by physical interaction and by phenotype and so must cooperate to coordinate dynein function in the cell.

Abstract

Eukaryotic cells use cytoskeletal motor proteins to transport many different intracellular cargos. Numerous kinesins and myosins have evolved to cope with the various transport needs that have arisen during eukaryotic evolution. Surprisingly, a single cytoplasmic dynein (a minus end-directed microtubule motor) carries out similarly diverse transport activities as the many different types of kinesin. How is dynein coupled to its wide range of cargos and how is it spatially and temporally regulated? The answer could lie in the several multifunctional adaptors, including dynactin, lissencephaly 1, nuclear distribution protein E (NUDE) and NUDE-like, Bicaudal D, Rod–ZW10–Zwilch and Spindly, that regulate dynein function and localization.

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Figure 1: Multiple factors cooperate to target dynein to microtubule plus ends and to its cargos.
Figure 2: Adaptor proteins couple dynein to multiple functions at the mitotic kinetochore.

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References

  1. Karki, S. & Holzbaur, E. L. Cytoplasmic dynein and dynactin in cell division and intracellular transport. Curr. Opin. Cell Biol. 11, 45–53 (1999).

    CAS  PubMed  Google Scholar 

  2. Vale, R. D. The molecular motor toolbox for intracellular transport. Cell 112, 467–480 (2003).

    CAS  PubMed  Google Scholar 

  3. Neuwald, A. F., Aravind, L., Spouge, J. L. & Koonin, E. V. AAA+: a class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res. 9, 27–43 (1999).

    CAS  PubMed  Google Scholar 

  4. Vaughan, K. T. & Vallee, R. B. Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued. J. Cell Biol. 131, 1507–1516 (1995).

    CAS  PubMed  Google Scholar 

  5. Karki, S. & Holzbaur, E. L. Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex. J. Biol. Chem. 270, 28806–28811 (1995).

    CAS  PubMed  Google Scholar 

  6. 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).

    CAS  PubMed  Google Scholar 

  7. Purohit, A., Tynan, S. H., Vallee, R. & Doxsey, S. J. Direct interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization. J. Cell Biol. 147, 481–492 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Farkasovsky, M. & Kuntzel, H. Cortical Num1p interacts with the dynein intermediate chain Pac11p and cytoplasmic microtubules in budding yeast. J. Cell Biol. 152, 251–262 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ha, J. et al. A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes. J. Cell Biol. 181, 1027–1039 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang, Z., Khan, S. & Sheetz, M. P. Single cytoplasmic dynein molecule movements: characterization and comparison with kinesin. Biophys. J. 69, 2011–2023 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Mallik, R., Carter, B. C., Lex, S. A., King, S. J. & Gross, S. P. Cytoplasmic dynein functions as a gear in response to load. Nature 427, 649–652 (2004).

    CAS  PubMed  Google Scholar 

  12. Reck-Peterson, S. L. et al. Single-molecule analysis of dynein processivity and stepping behavior. Cell 126, 335–348 (2006). Using recombinant dynein from S. cerevisiae , the authors directly observe the motion of single molecules of dynein for the first time, showing that it is a processive motor that requires dimerization for processivity. Their data strongly suggest that alternating steps of the dynein heads drive motility.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Gennerich, A. & Vale, R. D. Walking the walk: how kinesin and dynein coordinate their steps. Curr. Opin. Cell Biol. 21, 59–67 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Gennerich, A., Carter, A. P., Reck-Peterson, S. L. & Vale, R. D. Force-induced bidirectional stepping of cytoplasmic dynein. Cell 131, 952–965 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Nan, X., Sims, P. A. & Xie, X. S. Organelle tracking in a living cell with microsecond time resolution and nanometer spatial precision. Chemphyschem 9, 707–712 (2008).

    CAS  PubMed  Google Scholar 

  16. Sims, P. A. & Xie, X. S. Probing dynein and kinesin stepping with mechanical manipulation in a living cell. Chemphyschem 13, 1511–1516 (2009).

    Google Scholar 

  17. Dixit, R., Ross, J. L., Goldman, Y. E. & Holzbaur, E. L. Differential regulation of dynein and kinesin motor proteins by tau. Science 319, 1086–1089 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Ross, J. L., Shuman, H., Holzbaur, E. L. & Goldman, Y. E. Kinesin and dynein-dynactin at intersecting microtubules: motor density affects dynein function. Biophys. J. 94, 3115–3125 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Toba, S., Watanabe, T. M., Yamaguchi-Okimoto, L., Toyoshima, Y. Y. & Higuchi, H. Overlapping hand-over-hand mechanism of single molecular motility of cytoplasmic dynein. Proc. Natl Acad. Sci. USA 103, 5741–5745 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Welte, M. A., Gross, S. P., Postner, M., Block, S. M. & Wieschaus, E. F. Developmental regulation of vesicle transport in Drosophila embryos: forces and kinetics. Cell 92, 547–557 (1998). The authors observe the motility and force generation of dynein- and kinesin-transported lipid droplets in living D. melanogaster embryos. Their data suggest that dynein and kinesin activities are coupled and that the protein Klarsicht might be involved in this coupling.

    CAS  PubMed  Google Scholar 

  21. Laib, J. A., Marin, J. A., Bloodgood, R. A. & Guilford, W. H. The reciprocal coordination and mechanics of molecular motors in living cells. Proc. Natl Acad. Sci. USA 106, 3190–3195 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ross, J. L., Ali, M. Y. & Warshaw, D. M. Cargo transport: molecular motors navigate a complex cytoskeleton. Curr. Opin. Cell Biol. 20, 41–47 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 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).

    CAS  PubMed  Google Scholar 

  24. Schroer, T. A. & Sheetz, M. P. Two activators of microtubule-based vesicle transport. J. Cell Biol. 115, 1309–1318 (1991).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  26. Adames, N. R. & Cooper, J. A. Microtubule interactions with the cell cortex causing nuclear movements in Saccharomyces cerevisiae. J. Cell Biol. 149, 863–874 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Lee, W. L., Kaiser, M. A. & Cooper, J. A. The offloading model for dynein function: differential function of motor subunits. J. Cell Biol. 168, 201–207 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lee, W. L., Oberle, J. R. & Cooper, J. A. The role of the lissencephaly protein Pac1 during nuclear migration in budding yeast. J. Cell Biol. 160, 355–364 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Sheeman, B. et al. Determinants of S. cerevisiae dynein localization and activation: implications for the mechanism of spindle positioning. Curr. Biol. 13, 364–372 (2003).

    CAS  PubMed  Google Scholar 

  30. Kardon, J. R., Reck-Peterson, S. L. & Vale, R. D. Regulation of the processivity and intracellular localization of Saccharomyces cerevisiae dynein by dynactin. Proc. Natl Acad. Sci. USA 106, 5669–5674 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Xiang, X., Zuo, W., Efimov, V. P. & Morris, N. R. Isolation of a new set of Aspergillus nidulans mutants defective in nuclear migration. Curr. Genet. 35, 626–630 (1999).

    CAS  PubMed  Google Scholar 

  33. Fischer, R. & Timberlake, W. E. Aspergillus nidulans apsA (anucleate primary sterigmata) encodes a coiled-coil protein required for nuclear positioning and completion of asexual development. J. Cell Biol. 128, 485–498 (1995).

    CAS  PubMed  Google Scholar 

  34. Xiang, X., Han, G., Winkelmann, D. A., Zuo, W. & Morris, N. R. Dynamics of cytoplasmic dynein in living cells and the effect of a mutation in the dynactin complex actin-related protein Arp1. Curr. Biol. 10, 603–606 (2000).

    CAS  PubMed  Google Scholar 

  35. Zhang, J., Li, S., Fischer, R. & Xiang, X. Accumulation of cytoplasmic dynein and dynactin at microtubule plus ends in Aspergillus nidulans is kinesin dependent. Mol. Biol. Cell 14, 1479–1488 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Hayashi, I., Wilde, A., Mal, T. K. & Ikura, M. Structural basis for the activation of microtubule assembly by the EB1 and p150Glued complex. Mol. Cell 19, 449–460 (2005).

    CAS  PubMed  Google Scholar 

  37. Honnappa, S. et al. Key interaction modes of dynamic +TIP networks. Mol. Cell 23, 663–671 (2006).

    CAS  PubMed  Google Scholar 

  38. Weisbrich, A. et al. Structure-function relationship of CAP-Gly domains. Nature Struct. Mol. Biol. 14, 959–967 (2007).

    CAS  Google Scholar 

  39. Hayashi, I., Plevin, M. J. & Ikura, M. CLIP170 autoinhibition mimics intermolecular interactions with p150Glued or EB1. Nature Struct. Mol. Biol. 14, 980–981 (2007). References 36–39 use structural and biochemical methods to define the interactions between CAP-Gly domains and both the zinc knuckle motif found in CLIP170 and the acidic C-terminal motif found in CLIP170, EB1 and α-tubulin. Competition and cooperation between these moderate affinity interactions are probably important to microtubule plus end tracking and its regulation.

    CAS  Google Scholar 

  40. Valetti, C. et al. Role of dynactin in endocytic traffic: effects of dynamitin overexpression and colocalization with CLIP-170. Mol. Biol. Cell 10, 4107–4120 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Lansbergen, G. et al. Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization. J. Cell Biol. 166, 1003–1014 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Vaughan, P. S., Miura, P., Henderson, M., Byrne, B. & Vaughan, K. T. A role for regulated binding of p150Glued to microtubule plus ends in organelle transport. J. Cell Biol. 158, 305–319 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Watson, P., Forster, R., Palmer, K. J., Pepperkok, R. & Stephens, D. J. Coupling of ER exit to microtubules through direct interaction of COPII with dynactin. Nature Cell Biol. 7, 48–55 (2005).

    CAS  PubMed  Google Scholar 

  44. Puls, I. et al. Mutant dynactin in motor neuron disease. Nature Genet. 33, 455–456 (2003).

    CAS  PubMed  Google Scholar 

  45. Lai, C. et al. The G59S mutation in p150glued causes dysfunction of dynactin in mice. J. Neurosci. 27, 13982–13990 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Levy, J. R. et al. A motor neuron disease-associated mutation in p150Glued perturbs dynactin function and induces protein aggregation. J. Cell Biol. 172, 733–745 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Chevalier-Larsen, E. S., Wallace, K. E., Pennise, C. R. & Holzbaur, E. L. Lysosomal proliferation and distal degeneration in motor neurons expressing the G59S mutation in the p150Glued subunit of dynactin. Hum. Mol. Genet. 17, 1946–1955 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Tokito, M. K., Howland, D. S., Lee, V. M. & Holzbaur, E. L. Functionally distinct isoforms of dynactin are expressed in human neurons. Mol. Biol. Cell 7, 1167–1180 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim, H. et al. Microtubule binding by dynactin is required for microtubule organization but not cargo transport. J. Cell Biol. 176, 641–651 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Dixit, R., Levy, J. R., Tokito, M., Ligon, L. A. & Holzbaur, E. L. Regulation of dynactin through the differential expression of p150Glued isoforms. J. Biol. Chem. 283, 33611–33619 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Lomakin, A. J. et al. CLIP-170-dependent capture of membrane organelles by microtubules initiates minus-end directed transport. Dev. Cell 17, 323–333 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  53. Muresan, V. et al. Dynactin-dependent, dynein-driven vesicle transport in the absence of membrane proteins: a role for spectrin and acidic phospholipids. Mol. Cell 7, 173–183 (2001).

    CAS  PubMed  Google Scholar 

  54. De Matteis, M. A. & Morrow, J. S. Spectrin tethers and mesh in the biosynthetic pathway. J. Cell Sci. 113, 2331–2343 (2000).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Rocha, N. et al. Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150Glued and late endosome positioning. J. Cell Biol. 185, 1209–1225 (2009). Through its conformational change in response to the cholesterol content of the membrane, ORPL1 regulates the association of dynein and dynactin with late endosomes and thus regulates their transport in response to cellular conditions.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Kumar, S., Zhou, Y. & Plamann, M. Dynactin-membrane interaction is regulated by the C-terminal domains of p150Glued. EMBO Rep. 2, 939–944 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Lee, I. H., Kumar, S. & Plamann, M. Null mutants of the neurospora actin-related protein 1 pointed-end complex show distinct phenotypes. Mol. Biol. Cell 12, 2195–2206 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Blangy, A., Arnaud, L. & Nigg, E. A. Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150. J. Biol. Chem. 272, 19418–19424 (1997).

    CAS  PubMed  Google Scholar 

  60. Deacon, S. W. et al. Dynactin is required for bidirectional organelle transport. J. Cell Biol. 160, 297–301 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Berezuk, M. A. & Schroer, T. A. Dynactin enhances the processivity of kinesin-2. Traffic 8, 124–129 (2007).

    CAS  PubMed  Google Scholar 

  62. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. King, S. J. & Schroer, T. A. Dynactin increases the processivity of the cytoplasmic dynein motor. Nature Cell Biol. 2, 20–24 (2000).

    CAS  PubMed  Google Scholar 

  64. Culver-Hanlon, T. L., Lex, S. A., Stephens, A. D., Quintyne, N. J. & King, S. J. A microtubule-binding domain in dynactin increases dynein processivity by skating along microtubules. Nature Cell Biol. 8, 264–270 (2006).

    CAS  PubMed  Google Scholar 

  65. Moore, J. K., Sept, D. & Cooper, J. A. Neurodegeneration mutations in dynactin impair dynein-dependent nuclear migration. Proc. Natl Acad. Sci. USA 106, 5147–5152 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Dobyns, W. B., Reiner, O., Carrozzo, R. & Ledbetter, D. H. Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270, 2838–2842 (1993).

    CAS  PubMed  Google Scholar 

  67. Vallee, R. B. & Tsai, J. W. The cellular roles of the lissencephaly gene LIS1, and what they tell us about brain development. Genes Dev. 20, 1384–1393 (2006).

    CAS  PubMed  Google Scholar 

  68. Xiang, X., Roghi, C. & Morris, N. R. Characterization and localization of the cytoplasmic dynein heavy chain in Aspergillus nidulans. Proc. Natl Acad. Sci. USA 92, 9890–9894 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Geiser, J. R. et al. Saccharomyces cerevisiae genes required in the absence of the CIN8-encoded spindle motor act in functionally diverse mitotic pathways. Mol. Biol. Cell 8, 1035–1050 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Efimov, V. P. & Morris, N. R. The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein. J. Cell Biol. 150, 681–688 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Feng, Y. et al. LIS1 regulates CNS lamination by interacting with mNudE, a central component of the centrosome. Neuron 28, 665–679 (2000).

    CAS  PubMed  Google Scholar 

  72. Niethammer, M. et al. NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron 28, 697–711 (2000).

    CAS  PubMed  Google Scholar 

  73. Sasaki, S. et al. A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system. Neuron 28, 681–696 (2000).

    CAS  PubMed  Google Scholar 

  74. Smith, D. S. et al. Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1. Nature Cell Biol. 2, 767–775 (2000).

    CAS  PubMed  Google Scholar 

  75. Liang, Y. et al. Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein. J. Cell Biol. 164, 557–566 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Swan, A., Nguyen, T. & Suter, B. Drosophila Lissencephaly-1 functions with Bic-D and dynein in oocyte determination and nuclear positioning. Nature Cell Biol. 1, 444–449 (1999).

    CAS  PubMed  Google Scholar 

  77. Han, G. et al. The Aspergillus cytoplasmic dynein heavy chain and NUDF localize to microtubule ends and affect microtubule dynamics. Curr. Biol. 11, 719–724 (2001).

    CAS  PubMed  Google Scholar 

  78. Li, J., Lee, W. L. & Cooper, J. A. NudEL targets dynein to microtubule ends through LIS1. Nature Cell Biol. 7, 686–690 (2005).

    CAS  PubMed  Google Scholar 

  79. Carvalho, P., Gupta, M. L. Jr, Hoyt, M. A. & Pellman, D. Cell cycle control of kinesin-mediated transport of Bik1 (CLIP-170) regulates microtubule stability and dynein activation. Dev. Cell 6, 815–829 (2004).

    CAS  PubMed  Google Scholar 

  80. Coquelle, F. M. et al. LIS1, CLIP-170's key to the dynein/dynactin pathway. Mol. Cell. Biol. 22, 3089–3102 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Efimov, V. P. Roles of NUDE and NUDF proteins of Aspergillus nidulans: insights from intracellular localization and overexpression effects. Mol. Biol. Cell 14, 871–888 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Markus, S. M., Punch, J. J. & Lee, W. L. Motor- and tail-dependent targeting of dynein to microtubule plus ends and the cell cortex. Curr. Biol. 19, 196–205 (2009). This study in S. cerevisiae shows that, unlike full length dynein, LIS1-mediated microtubule plus end targeting of the dynein motor domain does not require NUDEL, suggesting that NUDEL is required only to prime dynein for LIS1 activity.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Feng, Y. & Walsh, C. A. Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron 44, 279–293 (2004).

    CAS  PubMed  Google Scholar 

  84. Shu, T. et al. Ndel1 operates in a common pathway with LIS1 and cytoplasmic dynein to regulate cortical neuronal positioning. Neuron 44, 263–277 (2004).

    CAS  PubMed  Google Scholar 

  85. Siller, K. H. & Doe, C. Q. Lis1/dynactin regulates metaphase spindle orientation in Drosophila neuroblasts. Dev. Biol. 319, 1–9 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Tanaka, T. et al. Lis1 and doublecortin function with dynein to mediate coupling of the nucleus to the centrosome in neuronal migration. J. Cell Biol. 165, 709–721 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Tsai, J. W., Chen, Y., Kriegstein, A. R. & Vallee, R. B. LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. J. Cell Biol. 170, 935–945 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Tsai, J. W., Bremner, K. H. & Vallee, R. B. Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nature Neurosci. 10, 970–979 (2007). Through observations of migrating neurons in situ , the authors make the surprising observation that the nucleus frequently lags the movement of the centrosome, rather than being tightly coupled as had been thought previously. Dynein and LIS1 contribute to the continuous centrosome movement and to saltatory nuclear movements through separate mechanisms.

    CAS  PubMed  Google Scholar 

  89. Gomes, E. R., Jani, S. & Gundersen, G. G. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121, 451–463 (2005).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Shen, Y. et al. Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev. Cell 14, 342–353 (2008).

    CAS  PubMed  Google Scholar 

  92. Faulkner, N. E. et al. A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function. Nature Cell Biol. 2, 784–791 (2000).

    CAS  PubMed  Google Scholar 

  93. Cockell, M. M., Baumer, K. & Gonczy, P. lis-1 is required for dynein-dependent cell division processes in C. elegans embryos. J. Cell Sci. 117, 4571–4582 (2004).

    CAS  PubMed  Google Scholar 

  94. Yang, Z. et al. Silencing mitosin induces misaligned chromosomes, premature chromosome decondensation before anaphase onset, and mitotic cell death. Mol. Cell. Biol. 25, 4062–4074 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Soukoulis, V. et al. Cytoplasmic LEK1 is a regulator of microtubule function through its interaction with the LIS1 pathway. Proc. Natl Acad. Sci. USA 102, 8549–8554 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Liang, Y. et al. Nudel modulates kinetochore association and function of cytoplasmic dynein in M phase. Mol. Biol. Cell 18, 2656–2666 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Vergnolle, M. A. & Taylor, S. S. Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes. Curr. Biol. 17, 1173–1179 (2007).

    CAS  PubMed  Google Scholar 

  98. Mesngon, M. T. et al. Regulation of cytoplasmic dynein ATPase by Lis1. J. Neurosci. 26, 2132–2139 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Steward, R. & Nusslein-Volhard, C. The genetics of the dorsal-Bicaudal-D region of Drosophila melanogaster. Genetics 113, 665–678 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  103. Delanoue, R. & Davis, I. Dynein anchors its mRNA cargo after apical transport in the Drosophila blastoderm embryo. Cell 122, 97–106 (2005).

    CAS  PubMed  Google Scholar 

  104. Navarro, C., Puthalakath, H., Adams, J. M., Strasser, A. & Lehmann, R. Egalitarian binds dynein light chain to establish oocyte polarity and maintain oocyte fate. Nature Cell Biol. 6, 427–435 (2004).

    CAS  PubMed  Google Scholar 

  105. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Matanis, T. et al. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nature Cell Biol. 4, 986–992 (2002).

    CAS  PubMed  Google Scholar 

  107. Hoogenraad, C. C. et al. Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. EMBO J. 22, 6004–6015 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. 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).

    PubMed  PubMed Central  Google Scholar 

  109. Pare, C. & Suter, B. Subcellular localization of Bic-D::GFP is linked to an asymmetric oocyte nucleus. J. Cell Sci. 113, 2119–2127 (2000).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Oh, J. & Steward, R. Bicaudal-D is essential for egg chamber formation and cytoskeletal organization in drosophila oogenesis. Dev. Biol. 232, 91–104 (2001).

    CAS  PubMed  Google Scholar 

  112. 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). The authors show that the Bicaudal D binding partner Egalitarian directly binds localization signals on mRNA, and they propose a general framework for the contribution of Bicaudal D to dynein cargo binding.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Bullock, S. L., Nicol, A., Gross, S. P. & Zicha, D. Guidance of bidirectional motor complexes by mRNA cargoes through control of dynein number and activity. Curr. Biol. 16, 1447–1452 (2006).

    CAS  PubMed  Google Scholar 

  114. 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). Spindly is identified as a kinetochore-specific regulator of cytoplasmic dynein.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Yang, Z., Tulu, U. S., Wadsworth, P. & Rieder, C. L. Kinetochore dynein is required for chromosome motion and congression independent of the spindle checkpoint. Curr. Biol. 17, 973–980 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Li, Y., Yu, W., Liang, Y. & Zhu, X. Kinetochore dynein generates a poleward pulling force to facilitate congression and full chromosome alignment. Cell Res. 17, 701–712 (2007).

    CAS  PubMed  Google Scholar 

  117. Tanaka, T. U. & Desai, A. Kinetochore-microtubule interactions: the means to the end. Curr. Opin. Cell Biol. 20, 53–63 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Gassmann, R. et al. A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex. Genes Dev. 22, 2385–2399 (2008). The authors characterize the C. elegans homologue of Spindly and propose a model for how Spindly, RZZ and dynein regulate the maturation of microtubule–kinetochore attachments.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Yamamoto, T. G., Watanabe, S., Essex, A. & Kitagawa, R. SPDL-1 functions as a kinetochore receptor for MDF-1 in Caenorhabditis elegans. J. Cell Biol. 183, 187–194 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Howell, B. J. et al. Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation. J. Cell Biol. 155, 1159–1172 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Wojcik, E. et al. Kinetochore dynein: its dynamics and role in the transport of the Rough deal checkpoint protein. Nature Cell Biol. 3, 1001–1007 (2001). References 120 and 121 present the initial evidence that dynein transports SAC proteins away from the kinetochore, thus silencing the checkpoint, and that the RZZ complex is involved in this process.

    CAS  PubMed  Google Scholar 

  122. Basto, R. et al. In vivo dynamics of the rough deal checkpoint protein during Drosophila mitosis. Curr. Biol. 14, 56–61 (2004).

    CAS  PubMed  Google Scholar 

  123. Chan, Y. W. et al. Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly. J. Cell Biol. 185, 859–874 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Whyte, J. et al. Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis. J. Cell Biol. 183, 819–834 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Hirose, H. et al. Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi. EMBO J. 23, 1267–1278 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Varma, D., Dujardin, D. L., Stehman, S. A. & Vallee, R. B. Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function. J. Cell Biol. 172, 655–662 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Starr, D. A., Williams, B. C., Hays, T. S. & Goldberg, M. L. ZW10 helps recruit dynactin and dynein to the kinetochore. J. Cell Biol. 142, 763–774 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Bates, M., Huang, B., Dempsey, G. T. & Zhuang, X. Multicolor super-resolution imaging with photo-switchable fluorescent probes. Science 317, 1749–1753 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Huang, B., Wang, W., Bates, M. & Zhuang, X. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science 319, 810–813 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Betzig, E. et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642–1645 (2006).

    CAS  PubMed  Google Scholar 

  131. Shtengel, G. et al. Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure. Proc. Natl Acad. Sci. USA 106, 3125–3130 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Reck-Peterson, S. L. & Vale, R. D. Molecular dissection of the roles of nucleotide binding and hydrolysis in dynein's AAA domains in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 101, 1491–1495 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Kon, T., Nishiura, M., Ohkura, R., Toyoshima, Y. Y. & Sutoh, K. Distinct functions of nucleotide-binding/hydrolysis sites in the four AAA modules of cytoplasmic dynein. Biochemistry 43, 11266–11274 (2004).

    CAS  PubMed  Google Scholar 

  134. Cho, C., Reck-Peterson, S. L. & Vale, R. D. Regulatory ATPase sites of cytoplasmic dynein affect processivity and force generation. J. Biol. Chem. 283, 25839–25845 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Gee, M. A., Heuser, J. E. & Vallee, R. B. An extended microtubule-binding structure within the dynein motor domain. Nature 390, 636–639 (1997).

    CAS  PubMed  Google Scholar 

  136. Burgess, S. A., Walker, M. L., Sakakibara, H., Knight, P. J. & Oiwa, K. Dynein structure and power stroke. Nature 421, 715–718 (2003).

    CAS  PubMed  Google Scholar 

  137. Carter, A. P. et al. Structure and functional role of dynein's microtubule-binding domain. Science 322, 1691–1695 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Kon, T. et al. Helix sliding in the stalk coiled coil of dynein couples ATPase and microtubule binding. Nature Struct. Mol. Biol. 16, 325–333 (2009).

    CAS  Google Scholar 

  139. Gibbons, I. R. et al. The affinity of the dynein microtubule-binding domain is modulated by the conformation of its coiled-coil stalk. J. Biol. Chem. 280, 23960–23965 (2005).

    CAS  PubMed  Google Scholar 

  140. Roberts, A. J. et al. AAA+ ring and linker swing mechanism in the dynein motor. Cell 136, 485–495 (2009). The authors use negative stain electron microscopy to map the position of the dynein linker domain and microtubule-binding stalk relative to the AAA ring in different nucleotide states and propose a mechanism for dynein motility based on movement of the linker across the face of the AAA ring.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Tai, C. Y., Dujardin, D. L., Faulkner, N. E. & Vallee, R. B. Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function. J. Cell Biol. 156, 959–968 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Stehman, S. A., Chen, Y., McKenney, R. J. & Vallee, R. B. NudE and NudEL are required for mitotic progression and are involved in dynein recruitment to kinetochores. J. Cell Biol. 178, 583–594 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. 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).

    CAS  PubMed  Google Scholar 

  144. Schafer, D. A., Gill, S. R., Cooper, J. A., Heuser, J. E. & Schroer, T. A. Ultrastructural analysis of the dynactin complex: an actin-related protein is a component of a filament that resembles F-actin. J. Cell Biol. 126, 403–412 (1994).

    CAS  PubMed  Google Scholar 

  145. Eckley, D. M. et al. Analysis of dynactin subcomplexes reveals a novel actin-related protein associated with the arp1 minifilament pointed end. J. Cell Biol. 147, 307–320 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Garces, J. A., Clark, I. B., Meyer, D. I. & Vallee, R. B. Interaction of the p62 subunit of dynactin with Arp1 and the cortical actin cytoskeleton. Curr. Biol. 9, 1497–1500 (1999).

    CAS  PubMed  Google Scholar 

  147. Vierula, P. J. & Mais, J. M. A gene required for nuclear migration in Neurospora crassa codes for a protein with cysteine-rich, LIM/RING-like domains. Mol. Microbiol. 24, 331–340 (1997).

    CAS  PubMed  Google Scholar 

  148. Imai, H., Narita, A., Schroer, T. A. & Maeda, Y. Two-dimensional averaged images of the dynactin complex revealed by single particle analysis. J. Mol. Biol. 359, 833–839 (2006).

    CAS  PubMed  Google Scholar 

  149. Moore, J. K., Li, J. & Cooper, J. A. Dynactin function in mitotic spindle positioning. Traffic 9, 510–527 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Kops, G. J. et al. ZW10 links mitotic checkpoint signaling to the structural kinetochore. J. Cell Biol. 169, 49–60 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Quintyne, N. J. et al. Dynactin is required for microtubule anchoring at centrosomes. J. Cell Biol. 147, 321–334 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. King, S. J., Brown, C. L., Maier, K. C., Quintyne, N. J. & Schroer, T. A. Analysis of the dynein-dynactin interaction in vitro and in vivo. Mol. Biol. Cell 14, 5089–5097 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Kim, M. H. et al. The structure of the N-terminal domain of the product of the lissencephaly gene Lis1 and its functional implications. Structure 12, 987–998 (2004).

    CAS  PubMed  Google Scholar 

  154. Tarricone, C. et al. Coupling PAF signaling to dynein regulation: structure of LIS1 in complex with PAF-acetylhydrolase. Neuron 44, 809–821 (2004).

    CAS  PubMed  Google Scholar 

  155. Derewenda, U. et al. The structure of the coiled-coil domain of ndel1 and the basis of its interaction with lis1, the causal protein of miller-dieker lissencephaly. Structure 15, 1467–1481 (2007).

    CAS  PubMed  Google Scholar 

  156. Yan, X. et al. Human Nudel and NudE as regulators of cytoplasmic dynein in poleward protein transport along the mitotic spindle. Mol. Cell. Biol. 23, 1239–1250 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Hebbar, S. et al. Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in neural stem cells. J. Cell Biol. 182, 1063–1071 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Hattori, M., Adachi, H., Tsujimoto, M., Arai, H. & Inoue, K. Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase. Nature 370, 216–218 (1994).

    CAS  PubMed  Google Scholar 

  159. Oh, J., Baksa, K. & Steward, R. Functional domains of the Drosophila bicaudal-D protein. Genetics 154, 713–724 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Stuurman, N. et al. Interactions between coiled-coil proteins: Drosophila lamin Dm0 binds to the bicaudal-D protein. Eur. J. Cell Biol. 78, 278–287 (1999).

    CAS  PubMed  Google Scholar 

  161. Wanschers, B. F. et al. A role for the Rab6B Bicaudal-D1 interaction in retrograde transport in neuronal cells. Exp. Cell Res. 313, 3408–3420 (2007).

    CAS  PubMed  Google Scholar 

  162. Siller, K. H., Serr, M., Steward, R., Hays, T. S. & Doe, C. Q. Live imaging of Drosophila brain neuroblasts reveals a role for Lis1/dynactin in spindle assembly and mitotic checkpoint control. Mol. Biol. Cell 16, 5127–5140 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Dzhindzhev, N. S., Rogers, S. L., Vale, R. D. & Ohkura, H. Distinct mechanisms govern the localisation of Drosophila CLIP-190 to unattached kinetochores and microtubule plus-ends. J. Cell Sci. 118, 3781–3790 (2005).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank S. Reck-Peterson, A. Carter, N. Bradshaw and E. Griffis for helpful discussions and editorial comments and apologize to those authors whose work we could not cite owing to space limitations. This work was supported by the National Institutes of Health (grant number 38499, R.D.V.), the National Science Foundation (J.R.K) and the Howard Hughes Medical Institute.

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  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Julia R. Kardon

  2. Department of Cellular and Molecular Pharmacology, University of California, San Francisco and the Howard Hughes Medical Institute, San Francisco, 94158, California, USA

    Ronald D. Vale

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Glossary

Axoneme

The bundled microtubule structure at the centre of eukaryotic cilia and flagella. Coordinated binding and release of the axonemal dyneins slides the microtubules relative to each other. This causes the axoneme to bend and drives ciliary and flagellar beating. Axonemes function as tracks for the motors involved in intraflagellar transport.

AAA+ ATPase

(ATPase associated with various cellular activities). A large family of ATPases, the functions of which are diverse, with many involved in the conformational remodelling of other proteins and complexes. AAA+ ATPases contain one or two characteristic ATP-binding domains, with additional function-specific domains. These AAA modules usually function as hexameric rings.

Coiled coil

A common structural motif in proteins, consisting of two or more α-helices that twist around each other and bury hydrophobic residues in the interface and form an overall rod-like structure.

Optical trap

An instrument that uses a focused laser beam to hold, move and monitor the position of microscopic dielectric objects. Optical traps can be used to measure the force production and nanoscale movements of molecular motors that have been conjugated to dielectric objects such as latex beads.

Protofilament

The end-to-end arrangement of tubulin dimers along the long axis of microtubules. Microtubules most commonly are composed of thirteen protofilaments.

Astral microtubule

A microtubule that radiates from the mitotic spindle poles to the cell cortex. Astral microtubules are involved in the positioning and alignment of the spindle poles during cell division.

Hypha

The branching filament that is the main mode of vegetative growth for filamentous fungi. During hyphal growth, hyphae elongate from their tips and position newly formed nuclei along the length of the new growth.

Cytoskeleton-associated protein Gly-rich

(Cap-Gly). A domain found in several microtubule-associated proteins, which binds the EEY/F motif found at the carboxyl terminus of α-tubulin and several microtubule plus end-associated proteins.

GTPase-activating protein

A protein that stimulates the intrinsic activity of a GTPase to hydrolyse GTP to GDP.

CopII coat

A complex consisting of SEC13, SEC23, SEC24 and SEC31. This coat complex functions in anterograde transport from the endoplasmic reticulum to the Golgi.

GTPase effector

A protein that binds specifically to the GTP-bound conformation of a GTPase.

Kinetochore

A large multiprotein complex that assembles onto the centromere of the chromosome and links it to the microtubules of the mitotic spindle. The kinetochore is also a signalling centre for many of the proteins that control the progression of mitosis.

WD40 repeat

A motif of 40 amino acids that contains a Trp and Asp dipeptide at its carboxyl terminus. This domain is found in many functionally diverse proteins and often mediates protein–protein interactions.

Centrosome

The principal microtubule-organizing centre of animal cells, an organelle that contains the centrioles and that anchors the minus end of microtubules.

Spindle assembly checkpoint

The mitotic signalling pathway that prevents chromosome separation until all kinetochores have formed microtubule attachments. The proteins involved in this pathway have to be localized at the kinetochore to ensure chromosome segregation, and their physical removal from attached kinetochores by dynein silences their signalling and allows chromosome separation to begin.

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Kardon, J., Vale, R. Regulators of the cytoplasmic dynein motor. Nat Rev Mol Cell Biol 10, 854–865 (2009). https://doi.org/10.1038/nrm2804

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