title: Collapsin response mediator protein switches RhoA and Rac1 morphology in N1E-115 neuroblastoma cells and is regulated by Rho kinase.
abstract: The formation and directional guidance of neurites involves dynamic regulation of Rho family GTPases. Rac and Cdc42 promote neurite outgrowth, whereas Rho activation causes neurite retraction. Here we describe a role for collapsin response mediator protein (Crmp-2), a neuronal protein implicated in axonal outgrowth and a component of the semaphorin 3A pathway, in switching GTPase signaling when expressed in combination with either dominant active Rac or Rho. In neuroblastoma N1E-115 cells, co-expression of Crmp-2 with dominant active RhoA V14 induced Rac morphology, cell spreading and ruffling (and the formation of neurites). Conversely, co-expression of Crmp-2 with dominant active Rac1 V12 inhibited Rac morphology, and in cells already expressing Rac1 V12, Crmp-2 caused localized peripheral collapse, involving Rho (and Cdc42) activation. Rho kinase was a pivotal regulator of Crmp-2; Crmp-2 phosphorylation was required for Crmp-2/Rac1 V12 inhibition, but not Crmp-2/RhoA V14 induction, of Rac morphology. Thus Crmp-2, regulated by Rho kinase, promotes outgrowth and collapse in response to active Rho and Rac, respectively, reversing their usual morphological effects and providing a mechanism for dynamic modulation of growth cone guidance.
authors.affiliation: Department of Neurochemistry, Institute of Neurology, University College London, 1 Wakefield Street, London WC1N IPJ, United Kingdom. C.Hall@ion.ucl.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Hall
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Jacobs
authors.forename: G
authors.initials: G
authors.lastname: Ferrari
authors.forename: N
authors.initials: N
authors.lastname: Cann
authors.forename: M
authors.initials: M
authors.lastname: Teo
authors.forename: C
authors.initials: C
authors.lastname: Monfries
authors.forename: L
authors.initials: L
authors.lastname: Lim
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005799:Genes, Dominant; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D040121:Semaphorin-3A; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D040121:Semaphorin-3A; C095114:collapsin response mediator protein-2; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein