LKB1-mediated spatial control of GSK3beta and adenomatous polyposis coli contributes to centrosomal forward movement and neuronal migration in the developing neocortex.
Neuronal migration is an essential process for the development of the cerebral cortex. We have previously shown that LKB1, an evolutionally conserved polarity kinase, plays a critical role in neuronal migration in the developing neocortex. Here we show that LKB1 mediates Ser9 phosphorylation of GSK3beta to inactivate the kinase at the leading process tip of migrating neurons in the developing neocortex. This enables the microtubule plus-end binding protein adenomatous polyposis coli (APC) to localize at the distal ends of microtubules in the tip, thereby stabilizing microtubules near the leading edge. We also show that LKB1 activity, Ser9 phosphorylation of GSK3beta, and APC binding to the distal ends of microtubules are required for the microtubule stabilization in the leading process tip, centrosomal forward movement, and neuronal migration. These findings suggest that LKB1-induced spatial control of GSK3beta and APC at the leading process tip mediates the stabilization of microtubules within the tip and is critical for centrosomal forward movement and neuronal migration in the developing neocortex.
Asada
Naoyuki
N
Molecular Genetics Research Laboratory, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Sanada
Kamon
K
D055372:AMP-Activated Protein Kinases; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology*; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D019579:Neocortex / Q000254:growth & development* / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D012694:Serine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases