Activation of Aurora-A is essential for neuronal migration via modulation of microtubule organization

Takako Takitoh, Kanako Kumamoto, Chen Chi Wang, Makoto Sato, Shiori Toba, Anthony Wynshaw-Boris, Shinji Hirotsune

研究成果: ジャーナルへの寄稿学術論文査読

27 被引用数 (Scopus)


Neuronal migration is a critical feature to ensure proper location and wiring of neurons during cortical development. Postmitotic neurons migrate from the ventricular zone into the cortical plate to establish neuronal lamina in an "inside-out" gradient of maturation. Here, we report that the mitotic kinase Aurora-A is critical for the regulation of microtubule organization during neuronal migration via an Aurora-A-NDEL1 pathway in the mouse. Suppression of Aurora-A activity by inhibitors or siRNA resulted in severe impairment of neuronal migration of granular neurons. In addition, in utero injection of the Aurora-A kinase-dead mutant provoked defective migration of cortical neurons. Furthermore, we demonstrated that suppression of Aurora-A impaired microtubule modulation in migrating neurons. Interestingly, suppression of CDK5 by an inhibitor or siRNA reduced Aurora-A activity and NDEL1 phosphorylation by Aurora-A, which led to defective neuronal migration. We found that CDK5RAP2 is a key molecule that mediates functional interaction and is essential for centrosomal targeting of Aurora-A. Our observations demonstrated novel and surprising cross talk between Aurora-A and CDK5 during neuronal migration.

ジャーナルJournal of Neuroscience
出版ステータス出版済み - 08-08-2012

All Science Journal Classification (ASJC) codes

  • 医学一般


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