<i>KIF5A</i> upregulation by <scp>FAK</scp> ‐mediated downregulation of epigenetic modifiers promotes mitochondrial dynamics in neuronal differentiation

Neuronal differentiation depends on mitochondrial transport and networking toward the developing axon and dendrites. Herein, we report that the motor protein kinesin family member 5A (KIF5A) is essential for neuronal maturation through regulation of mitochondrial structure and dynamics. Focal adhesion kinase (FAK) signaling promotes differentiation through enhanced expression of KIF5A and downregulation of epigenetic modifiers, DNMT1 and KDM5A. FAK activity is phosphorylation-dependent to facilitate neuronal differentiation by KIF5A and repression of DNMT1 and KDM5A. This is the first report showing that FAK signaling controls epigenetic regulation of motor proteins by downregulation of epigenetic modifiers. Thus, molecular mechanisms for neurodevelopment and plausible therapeutic targets against neurodegenerative disorders are explored in this article.