title: Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.
abstract: During their migration, cerebellar granule cells switch from a tangential to a radial mode of migration. We have previously demonstrated that this involves the transmembrane semaphorin Sema6A. We show here that plexin-A2 is the receptor that controls Sema6A function in migrating granule cells. In plexin-A2-deficient (Plxna2(-/-)) mice, which were generated by homologous recombination, many granule cells remained in the molecular layer, as we saw in Sema6a mutants. A similar phenotype was observed in mutant mice that were generated by mutagenesis with N-ethyl-N-nitrosourea and had a single amino-acid substitution in the semaphorin domain of plexin-A2. We found that this mutation abolished the ability of Sema6A to bind to plexin-A2. Mouse chimera studies further suggested that plexin-A2 acts in a cell-autonomous manner. We also provide genetic evidence for a ligand-receptor relationship between Sema6A and plexin-A2 in this system. Using time-lapse video microscopy, we found that centrosome-nucleus coupling and coordinated motility were strongly perturbed in Sema6a(-/-) and Plxna2(-/-) granule cells. This suggests that semaphorin-plexin signaling modulates cell migration by controlling centrosome positioning.
authors.affiliation: Centre National de la Recherche Scientifique, UMR7102, 9 Quai Saint-Bernard, Paris F-75005, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Renaud
authors.forename: Géraldine
authors.initials: G
authors.lastname: Kerjan
authors.forename: Itsuko
authors.initials: I
authors.lastname: Sumita
authors.forename: Yvrick
authors.initials: Y
authors.lastname: Zagar
authors.forename: Virginie
authors.initials: V
authors.lastname: Georget
authors.forename: Doyeun
authors.initials: D
authors.lastname: Kim
authors.forename: Coralie
authors.initials: C
authors.lastname: Fouquet
authors.forename: Kazunori
authors.initials: K
authors.lastname: Suda
authors.forename: Makoto
authors.initials: M
authors.lastname: Sanbo
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Suto
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ackerman
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Mitchell
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C492113:Plxna2 protein, mouse; D011956:Receptors, Cell Surface; C504203:Sema6a protein, mouse; D039961:Semaphorins