Neurabin II mediates doublecortin-dephosphorylation on actin filaments.

Mutations in the human Doublecortin (DCX) gene cause X-linked lissencephaly, a neuronal migration disorder. DCX binds to microtubules and actin filaments. Association of Dcx with F-actin is regulated by site-specific phosphorylation and by neurabin II, an F-actin binding protein that also binds to Dcx. We show here that neurabin II mediates dephosphorylation of Dcx by protein phosphatase 1 (PP1). Furthermore, overexpression of PP1 reduces Dcx phosphorylation and decreases Dcx binding to F-actin. By contrast, abolishing PP1 binding to neurabin II maintains phosphorylation levels of Dcx, leading to a retention of Dcx at F-actin. We suggest that a dynamic regulation of Dcx mediated by neurabin II regulates the translocation of Dcx from F-actin to microtubules and vice versa.