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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.

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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.

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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.

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  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

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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.

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Correspondence to Tadashi Uemura.

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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

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