Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33.
Collapsin, a member of the newly recognized semaphorin family, contributes to axonal pathfinding during neural development by inhibiting growth cone extension. The mechanism of collapsin action is poorly understood. Here we use a Xenopus laevis oocyte expression system to identify molecules involved in collapsin signalling, because several experiments have raised the possibility that heterotrimeric GTP-binding proteins might participate in these events. A collapsin response mediator protein of relative molecular mass (M(r)) 62K (CRMP-62) required for collapsin-induced inward currents in X. laevis oocytes is isolated. CRMP-62 shares homology with UNC-33, a nematode neuronal protein required for appropriately directed axonal extension. CRMP-62 is localized exclusively in the developing chick nervous system. Introduction of anti-CRMP-62 antibodies into dorsal root ganglion neurons blocks collapsin-induced growth cone collapse. CRMP-62 appears to be an intracellular component of a signalling cascade initiated by an unidentified transmembrane collapsin-binding protein.
Goshima
Y
Y
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nakamura
F
F
Strittmatter
P
P
Strittmatter
S M
SM
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002642:Chick Embryo; D019204:GTP-Binding Proteins / Q000502:physiology; D005727:Ganglia, Spinal / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology*; D015801:Helminth Proteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D040121:Semaphorin-3A; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014982:Xenopus laevis
D029742:Caenorhabditis elegans Proteins; D006023:Glycoproteins; D015801:Helminth Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D040121:Semaphorin-3A; D010566:Virulence Factors, Bordetella; C095114:collapsin response mediator protein-2; C078652:unc-33 protein, C elegans; D019204:GTP-Binding Proteins