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.
Tsukada
Miki
M
Max-Planck-Institute for Experimental Endocrinology, Feodor-Lynen-Strasse 7, D-30625 Hannover, Germany. miki.tsukada@mpihan.mpg.de
Prokscha
Alexander
A
Eichele
Gregor
G
D008841:Actin Cytoskeleton / Q000201:enzymology*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D017434:Protein Structure, Tertiary; D000099273:Neurabins
D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D048056:Mitogen-Activated Protein Kinase 9; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D000099273:Neurabins; C000714328:DCX protein, human; C000714847:Dcx protein, mouse