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Tubulin tyrosination navigates the kinesin-1 motor domain to axons

Nature Neuroscience volume 12, pages 559567 (2009) | Download Citation

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Abstract

Neurons form distinctive axonal and dendritic compartments that are important for directional signaling, but the mechanisms that discriminate between axons and dendrites remain elusive. Previous studies have demonstrated that the kinesin-1 motor domain is capable of distinguishing the axon from dendrites. Here we found that the amino acid substitutions in the beta5-loop8 region transformed truncated kinesin-1 from a uni-destination (that is, the axon-specific destination) to a bi-destination (that is, axons and dendrites) state. Furthermore, tyrosinated tubulins that are abundant in somatodendrites prevent the wild-type kinesin-1 from binding to microtubules, whereas the bi-destination–type kinesin-1 does not have this inhibition. Consistently, inhibition of tubulin tyrosination in rat hippocampal neurons resulted in the distribution of truncated kinesin-1 in both axons and dendrites. Our study identifies a molecular mechanism that discriminates the axonal microtubules from somatodendritic microtubules, as well as a previously unknown linkage between tubulin modification and polarized trafficking in neurons.

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Acknowledgements

We are grateful to M. Kikkawa for his help with the electron microscopy and for valuable discussions. We also thank A. Bonni and N. Ohkawa for critical reading of the manuscript, T. Funatsu, S. Uemura and M. Tsunoda for valuable discussions, K. Yasutake and M. Arai for help with primary cultures, Y. Hatanaka and M. Takamatsu for help with preparing constructs, and the Department of Molecular Anatomy, Hamamatsu University School of Medicine and the Molecular Gerontology Group at the Mitsubishi Kagaku Institute of Life Sciences for various forms of help. This work was supported in part by Grants-In-Aid for Young Scientists S (M.S.) and B (Y.K.) and by a grant from the Mitsubishi Kagaku Institute of Life Sciences.

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  1. Department of Molecular Anatomy, Hamamatsu University School of Medicine, Handayama, Shizuoka, Japan.

    • Yoshiyuki Konishi
    •  & Mitsutoshi Setou
  2. Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo, Japan.

    • Yoshiyuki Konishi
    •  & Mitsutoshi Setou

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Y.K. conducted all experiments with technical assistances and wrote the manuscript. M.S. supervised the project.

Corresponding authors

Correspondence to Yoshiyuki Konishi or Mitsutoshi Setou.

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DOI

https://doi.org/10.1038/nn.2314