Abstract
Orchestrated remodelling of the cytoskeketon is prominent during neurite extension. In contrast with the extensive characterization of actin filament regulation, little is known about the dynamics of microtubules during neurite extension. Here we identify an atypical protein kinase C (aPKC)–Aurora A–NDEL1 pathway that is crucial for the regulation of microtubule organization during neurite extension. aPKC phosphorylates Aurora A at Thr 287 (T287), which augments interaction with TPX2 and facilitates activation of Aurora A at the neurite hillock, followed by phosphorylation of NDEL1 at S251 and recruitment. Suppression of aPKC, Aurora A or TPX2, or disruption of Ndel1, results in severe impairment of neurite extension. Analysis of microtubule dynamics with a microtubule plus-end marker revealed that suppression of the aPKC–Aurora A–NDEL1 pathway resulted in a significant decrease in the frequency of microtubule emanation from the microtubule organizing centre (MTOC), suggesting that Aurora A acts downstream of aPKC. These findings demonstrate a surprising role of aPKC–Aurora A–NDEL1 pathway in microtubule remodelling during neurite extension.
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Acknowledgements
We thank Yukimi Kira, Yoriko Yabunaka, Gaku Kuwabara, Toshiyuki Kawashima and Takako Takitho for technical support, and Hiromichi Nishimura and Keiko Fujimoto for mouse breeding. This work was also supported by the Osaka Community Foundation to D.M. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan to S.H. This work was also supported by the Cell Science Research Foundation, the Japan Spina Bifida and Hydrocephalus Research Foundation, the Takeda Science Foundation and the Hoh-ansha Foundation to S.H, and National Institutes of Health grants NS41030 and HD47380 to A.W.-B.
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D.M., M.Y., Y.S. and A.S. performed the experimental work, Y.M.-K., S.O. and H.S. conducted data analysis, and A.W.-B. and S.H. performed project planning and wrote the manuscript.
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Mori, D., Yamada, M., Mimori-Kiyosue, Y. et al. An essential role of the aPKC–Aurora A–NDEL1 pathway in neurite elongation by modulation of microtubule dynamics. Nat Cell Biol 11, 1057–1068 (2009). https://doi.org/10.1038/ncb1919
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DOI: https://doi.org/10.1038/ncb1919
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