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Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons

Nature Cell Biology volume 10, pages 1172–1180 (2008)Cite this article

Abstract

Axons and dendrites differ in both microtubule organization and in the organelles and proteins they contain. Here we show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented uniformly plus-end-distal; however, without dynein, axons contain both plus- and minus-end distal microtubules. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal microtubules are no longer uniform in polarity.

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Figure 1: dlic21157 functions cell-autonomously to regulate dendrite and axon development.
Figure 2: Loss of dynein function alters Golgi outpost distribution.
Figure 3: Localization of endosomes and Ppk depends on dynein.
Figure 4: Mislocalization of Nod–β-gal, but not Kin–β-gal, in dynein mutant neurons.
Figure 5: Mixed orientation of axonal microtubules in dic1229/dicts neurons revealed by EB1–GFP.

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Acknowledgements

We would like to thank T. Uemura, F.B. Gao, L. Luo, R. Warrior, T. Hays and the Bloomington Stock Center for fly stocks; W. Song, C. Han, S. Zhu, P. Soba, J. Parrish, J. Kardon and S. Reck-Peterson for helpful suggestions and comments on the manuscript, and members of the Jan Lab for stimulating discussions. We thank T. Uemura for communicating results before publication. This work was supported by Kirschstein NRSA fellowships F32-MH75223 (Y. Zheng.), F32-HD53199 (J.W.), an NIH Pathway to Independence Award K99MH080599 (B.Y.), a graduate fellowship from Genentech and the Sandler Family Supporting Foundation (Y. Zhang) and NIH grants R01NS40929 and R01NS47200 (Y.N.J.). Y.N.J. and L.Y.J. are Investigators of the Howard Hughes Medical Institute.

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  1. Yi Zheng and Jill Wildonger: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, 94143, CA, USA

    Yi Zheng, Jill Wildonger, Bing Ye, Ye Zhang, Angela Kita, Susan H. Younger, Sabina Zimmerman, Lily Yeh Jan & Yuh Nung Jan

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Contributions

Y. Zheng, J.W., S.H.Y. and Y.N.J. conceived and designed the project; Y. Zheng, J.W., A.K. and S.H.Y. carried out the genetic screen; B.Y.; Y. Zhang completed the Golgi outpost analysis and S.Z. analysed the EB1–GFP movies; Y. Zheng and J.W. performed all other experiments and contributed equally to this work; Y. Zheng, J.W. L.Y.J. and Y.N.J. wrote the paper; all authors read and edited the manuscript.

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Correspondence to Yuh Nung Jan.

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Zheng, Y., Wildonger, J., Ye, B. et al. Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. Nat Cell Biol 10, 1172–1180 (2008). https://doi.org/10.1038/ncb1777

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