title: CLASP2 Links Reelin to the Cytoskeleton during Neocortical Development.
abstract: The Reelin signaling pathway plays a crucial role in regulating neocortical development. However, little is known about how Reelin controls the cytoskeleton during neuronal migration. Here, we identify CLASP2 as a key cytoskeletal effector in the Reelin signaling pathway. We demonstrate that CLASP2 has distinct roles during neocortical development regulating neuron production and controlling neuron migration, polarity, and morphogenesis. We found downregulation of CLASP2 in migrating neurons leads to mislocalized cells in deeper cortical layers, abnormal positioning of the centrosome-Golgi complex, and aberrant length/orientation of the leading process. We discovered that Reelin regulates several phosphorylation sites within the positively charged serine/arginine-rich region that constitute consensus GSK3β phosphorylation motifs of CLASP2. Furthermore, phosphorylation of CLASP2 regulates its interaction with the Reelin adaptor Dab1 and this association is required for CLASP2 effects on neurite extension and motility. Together, our data reveal that CLASP2 is an essential Reelin effector orchestrating cytoskeleton dynamics during brain development.
authors.affiliation: Department of Biology, Boston University, 24 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Dillon
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Tyler
authors.affiliation: Department of Biology, Boston University, 24 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Kerilyn C
authors.initials: KC
authors.lastname: Omuro
authors.affiliation: Department of Biology, Boston University, 24 Cummington Mall, Boston, MA 02215, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kambouris
authors.affiliation: Department of Biology, Boston University, 24 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Camila
authors.initials: C
authors.lastname: Tyminski
authors.affiliation: Department of Biology, Boston University, 24 Cummington Mall, Boston, MA 02215, USA.
authors.forename: Shawna
authors.initials: S
authors.lastname: Henry
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
authors.forename: Tarik F
authors.initials: TF
authors.lastname: Haydar
authors.affiliation: Department of Biology, Boston University, 24 Cummington Mall, Boston, MA 02215, USA. Electronic address: ub1@bu.edu.
authors.forename: Uwe
authors.initials: U
authors.lastname: Beffert
authors.affiliation: Department of Biology, Boston University, 24 Cummington Mall, Boston, MA 02215, USA. Electronic address: aho1@bu.edu.
authors.forename: Angela
authors.initials: A
authors.lastname: Ho
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008869:Microtubule-Associated Proteins / Q000378:metabolism* / Q000502:physiology*; D019579:Neocortex / Q000254:growth & development* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: C506523:CLASP2 protein, mouse; D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: CLASP2; GSK3beta; Reelin; cortical development; cytoskeleton; microtubule; plus-end