Article abstract
Nature Cell Biology 11, 1057 - 1068 (2009)
Published online: 9 August 2009 | doi:10.1038/ncb1919
An essential role of the aPKC–Aurora A–NDEL1 pathway in neurite elongation by modulation of microtubule dynamics
Daisuke Mori1, Masami Yamada1, Yuko Mimori-Kiyosue2, Yasuhito Shirai3, Atsushi Suzuki4, Shigeo Ohno4, Hideaki Saya5, Anthony Wynshaw-Boris6 & Shinji Hirotsune1
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.
- Department of Genetic Disease Research, Osaka City University Graduate School of Medicine Asahi-machi 1-4-3 Abeno, Osaka 545-8585, Japan.
- Research Group for Cytoskeleton and Cell Motility, KAN Research Institute, Inc. 3F, Kobe MI R&D Center 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
- Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657–8501, Japan.
- Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
- Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinanomach 35 Shinjuku, Tokyo, Japan.
- UCSF School of Medicine, Department of Pediatrics and Institute for Human Genetics, San Francisco, California 94143, USA.
Correspondence to: Shinji Hirotsune1 e-mail: shinjih@med.osaka-cu.ac.jp
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