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.

  • Letter
  • Published:

Spatial control of branching within dendritic arbors by dynein-dependent transport of Rab5-endosomes

Nature Cell Biology volume 10, pages 1164–1171 (2008)Cite this article

Abstract

Dendrites allow neurons to integrate sensory or synaptic inputs, and the spatial disposition and local density of branches within the dendritic arbor limit the number and type of inputs1,2. Drosophila melanogaster dendritic arborization (da) neurons provide a model system to study the genetic programs underlying such geometry in vivo. Here we report that mutations of motor-protein genes, including a dynein subunit gene (dlic) and kinesin heavy chain (khc), caused not only downsizing of the overall arbor, but also a marked shift of branching activity to the proximal area within the arbor. This phenotype was suppressed when dominant-negative Rab5 was expressed in the mutant neurons, which deposited early endosomes in the cell body. We also showed that 1) in dendritic branches of the wild-type neurons, Rab5-containing early endosomes were dynamically transported and 2) when Rab5 function alone was abrogated, terminal branches were almost totally deleted. These results reveal an important link between microtubule motors and endosomes in dendrite morphogenesis.

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

Figure 1: dlic mutations caused abnormal dendritic and axonal morphogenesis.
Figure 2: dlic encodes dynein light intermediate chain.
Figure 3: Distribution and motility of early endosomes in dendrites and altered distribution and morphology of early endosomes in dlic clones.
Figure 4: Loss of Rab5 function reduced the number of dendritic branches.
Figure 5: Loss of kinesin heavy chain (khc) resulted in a phenotype similar to that of the dlic clone.

Similar content being viewed by others

References

  1. Jan, Y. N. & Jan, L. Y. The control of dendrite development. Neuron 40, 229–242 (2003).

    Article  CAS  Google Scholar 

  2. London, M. & Hausser, M. Dendritic computation. Annu. Rev. Neurosci. 28, 503–532 (2005).

    Article  CAS  Google Scholar 

  3. Grueber, W. B., Jan, L. Y. & Jan, Y. N. Tiling of the Drosophila epidermis by multidendritic sensory neurons. Development 129, 2867–2878 (2002).

    CAS  PubMed  Google Scholar 

  4. Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22, 451–461 (1999).

    Article  CAS  Google Scholar 

  5. Goldstein, L. S. & Gunawardena, S. Flying through the Drosophila cytoskeletal genome. J. Cell Biol. 150, 63–68 (2000).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Bowman, A. B. et al. Drosophila roadblock and Chlamydomonas LC7: a conserved family of dynein-associated proteins involved in axonal transport, flagellar motility, and mitosis. J. Cell Biol. 146, 165–180 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu, Z., Steward, R. & Luo, L. Drosophila Lis1 is required for neuroblast proliferation, dendritic elaboration and axonal transport. Nature Cell Biol. 2, 776–783 (2000).

    Article  CAS  Google Scholar 

  10. Rolls, M. M. et al. Polarity and intracellular compartmentalization of Drosophila neurons. Neural Develop. 2, 7 (2007).

    Article  Google Scholar 

  11. Stowers, R. S., Megeath, L. J., Gorska-Andrzejak, J., Meinertzhagen, I. A. & Schwarz, T. L. Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36, 1063–1077 (2002).

    Article  CAS  Google Scholar 

  12. Zerial, M. & McBride, H. Rab proteins as membrane organizers. Nature Rev. Mol. Cell Biol. 2, 107–117 (2001).

    Article  CAS  Google Scholar 

  13. Welte, M. A. Bidirectional transport along microtubules. Curr. Biol. 14, 525–537 (2004).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Wucherpfennig, T., Wilsch-Brauninger, M. & Gonzalez-Gaitan, M. Role of Drosophila Rab5 during endosomal trafficking at the synapse and evoked neurotransmitter release. J. Cell Biol. 161, 609–624 (2003).

    Article  CAS  Google Scholar 

  16. Shin, H. W. et al. An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. J. Cell Biol. 170, 607–618 (2005).

    Article  CAS  Google Scholar 

  17. Entchev, E. V., Schwabedissen, A. & Gonzalez-Gaitan, M. Gradient formation of the TGF-β homolog Dpp. Cell 103, 981–991 (2000).

    Article  CAS  Google Scholar 

  18. Shimizu, H., Kawamura, S. & Ozaki, K. An essential role of Rab5 in uniformity of synaptic vesicle size. J. Cell Sci. 116, 3583–3590 (2003).

    Article  CAS  Google Scholar 

  19. Hirokawa, N. & Takemura, R. Molecular motors and mechanisms of directional transport in neurons. Nature Rev. Neurosci. 6, 201–214 (2005).

    Article  CAS  Google Scholar 

  20. Goldstein, L. S. Do disorders of movement cause movement disorders and dementia? Neuron 40, 415–425 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Miki, H., Setou, M., Kaneshiro, K. & Hirokawa, N. All kinesin superfamily protein, KIF, genes in mouse and human. Proc. Natl Acad. Sci. USA 98, 7004–7011 (2001).

    Article  CAS  Google Scholar 

  23. Brendza, R. P., Serbus, L. R., Saxton, W. M. & Duffy, J. B. Posterior localization of dynein and dorsal-ventral axis formation depend on kinesin in Drosophila oocytes. Curr. Biol. 12, 1541–1545 (2002).

    Article  CAS  Google Scholar 

  24. Lenz, J. H., Schuchardt, I., Straube, A. & Steinberg, G. A dynein loading zone for retrograde endosome motility at microtubule plus-ends. EMBO J. 25, 2275–2286 (2006).

    Article  CAS  Google Scholar 

  25. Ye, B. et al. Growing dendrites and axons differ in their reliance on the secretory pathway. Cell 130, 717–729 (2007).

    Article  CAS  Google Scholar 

  26. Miaczynska, M., Pelkmans, L. & Zerial, M. Not just a sink: endosomes in control of signal transduction. Curr. Opin. Cell Biol. 16, 400–406 (2004).

    Article  CAS  Google Scholar 

  27. Sweeney, N. T., Brenman, J. E., Jan, Y. N. & Gao, F. B. The coiled-coil protein shrub controls neuronal morphogenesis in Drosophila. Curr. Biol. 16, 1006–1011 (2006).

    Article  CAS  Google Scholar 

  28. Gruenberg, J. & Stenmark, H. The biogenesis of multivesicular endosomes. Nature Rev. Mol. Cell Biol. 5, 317–323 (2004).

    Article  CAS  Google Scholar 

  29. Pfister, K. K. et al. Genetic analysis of the cytoplasmic dynein subunit families. PLoS Genet. 2, e1 (2006).

    Article  Google Scholar 

  30. Sugimura, K. et al. Distinct developmental modes and lesion-induced reactions of dendrites of two classes of Drosophila sensory neurons. J. Neurosci. 23, 3752–3760 (2003).

    Article  CAS  Google Scholar 

  31. Brechbiel, J. L. & Gavis, E. R. Spatial regulation of nanos is required for its function in dendrite morphogenesis. Curr. Biol. 18, 745–750 (2008).

    Article  CAS  Google Scholar 

  32. Wu, M. N. et al. Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo. Neuron 23, 593–605 (1999).

    Article  CAS  Google Scholar 

  33. Funayama, R., Saito, M., Tanobe, H. & Ishikawa, F. Loss of linker histone H1 in cellular senescence. J. Cell Biol. 175, 869–880 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The reagents were provided by the Developmental Studies Hybridoma Bank at the University of Iowa, the Bloomington Stock Center, the Drosophila Genetic Resource Center at Kyoto Institute of Technology, J. Knoblich, D. Bilder, L. Luo, Y. N. Jan, H. Shimizu and W. Saxton. We thank Yuh-Nung Jan for communicating data before publication. We are grateful to K. Sugimura, K. Kousaka, T. Kiyomitsu, C. Obuse, M. Sone, Y. Okada, E. Gavis and M. Ohno for their technical advice and encouragement; T. Harumoto and S. Yonehara for allowing us to use their equipment; Y. Miyake and M. Futamata for their technical assistance. This work was supported by grants from the programs Grants-in-Aid for Scientific Research on Priority Areas-Molecular Brain Science (17024025 to T.U.) and for Cancer Research (to F.I. and M.S.) of the MEXT of Japan, by a Wellcome Trust Senior Research Fellowship (to H.O.), and by a NARSAD Young Investigator Award (to M.M.R.). D.S is a recipient of a Fellowship of the Japan Society for the Promotion of Science for Junior Scientists.

Author information

Author notes

  1. Melissa M. Rolls

    Present address: Current address: Department of Biochemistry and Molecular Biology, Penn State, University Park, Pennsylvania, USA.,

Authors and Affiliations

  1. Department of Biophysics, Graduate School of Science, Sakyo-ku, 606-8507, Kyoto, Japan

    Daisuke Satoh

  2. Laboratory of Cell Recognition and Pattern Formation, Sakyo-ku, 606-8507, Kyoto, Japan

    Daichi Sato, Taiichi Tsuyama & Tadashi Uemura

  3. Laboratory of Cell Cycle Regulation, Graduate School of Biostudies, South Campus Research Building (Building G), Kyoto University, Yoshida Konoe-cho, Sakyo-ku, 606-8507, Kyoto, Japan

    Motoki Saito & Fuyuki Ishikawa

  4. Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, United Kingdom

    Hiroyuki Ohkura

  5. Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, USA

    Melissa M. Rolls

Authors
  1. Daisuke Satoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daichi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taiichi Tsuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Motoki Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyuki Ohkura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Melissa M. Rolls
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fuyuki Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tadashi Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.Satoh carried out most of the experiments; D.Sato, T.T., M.S. and F.I. assisted with some experiments; H.O. and M.M.R. supplied reagents. D.Satoh and T.U. wrote the paper.

Corresponding author

Correspondence to Tadashi Uemura.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Figures S1, S2, S3, S4, S5, S6, S7, S8 and Supplementary Methods (PDF 2647 kb)

Supplementary Information

Supplementary Movie 1 (MOV 5837 kb)

Supplementary Information

Supplementary Movie 2 (MOV 5369 kb)

Supplementary Information

Supplementary Movie 3 (MOV 8705 kb)

Supplementary Information

Supplementary Movie 4 (MOV 7524 kb)

Supplementary Information

Supplementary Movie 5 (MOV 2073 kb)

Supplementary Information

Supplementary Movie 6 (MOV 4420 kb)

Supplementary Information

Supplementary Movie 7 (MOV 4420 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Satoh, D., Sato, D., Tsuyama, T. et al. Spatial control of branching within dendritic arbors by dynein-dependent transport of Rab5-endosomes. Nat Cell Biol 10, 1164–1171 (2008). https://doi.org/10.1038/ncb1776

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1776

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