Abundant Focal Adhesion Kinase Causes Aberrant Neuronal Migration Via Its Phosphorylation at Tyr925

Abstract

The process of neuronal migration is precisely regulated by different molecules during corticogenesis. The FAK (focal adhesion kinase) plays a critical role in embryogenesis and is involved in cell motility through focal adhesions, but the underlying mechanisms on inordinate expression are unclear. To investigate the effect of FAK overexpression on neuronal migration spatiotemporally, mice FAK was transfected into the neurons in vivo by electroporation. Results showed that exogenous FAK distributed in the cytoplasm (in vivo) and co-localized with vinculin (in vitro) and induced aberrant neuronal migration via phosphorylation of FAK at Tyr925 during cerebral cortex development. Meanwhile, FAK Y925F mutant also induced aberrant neuronal migration like inordinate FAK/GFP phenotype. All these results implied that FAK-induced abnormal phenotype depended on phosphorylation of FAK at Tyr925, and this demonstrated that the overexpression of FAK impaired neuronal migration through its phosphorylation and activity of FAK during corticogenesis.

Keywords: Focal adhesion kinase; In utero electroporation; Mutant; Neuronal migration; Phosphorylation.