Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration

Zhigang Xie, Kamon Sanada, Benjamin Adam Samuels, Heather Shih, Li Huei Tsai

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

Abstract

The serine/threonine kinase Cdk5 plays an essential role in neuronal positioning during corticogenesis, but the underlying mechanisms are unknown. In nonneuronal cells, the tyrosine kinase FAK is a major regulator of cell motility through focal adhesions. It is unclear whether FAK plays a role in brain development. Here, we show that FAK phosphorylation by Cdk5 at S732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, S732-phosphorylated FAK is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant FAK S732A results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo. These observations are reminiscent of what is seen in the Cdk5-deficient mice. Taken together, these results suggest that Cdk5 phosphorylation of FAK is critical for neuronal migration through regulation of a microtubule fork important for nuclear translocation.

Original languageEnglish (US)
Pages (from-to)469-482
Number of pages14
JournalCell
Volume114
Issue number4
DOIs
StatePublished - Aug 22 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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