title: CRMP4 mediates MAG-induced inhibition of axonal outgrowth and protection against Vincristine-induced axonal degeneration.
abstract: Suppression of inhibition of axonal outgrowth and promotion of axonal protection from progressive axonal degeneration are both therapeutic strategies for the treatment of neuronal diseases characterized by axonal loss. Myelin-associated inhibitors (MAIs) have been shown to suppress axonal outgrowth, but a specific MAI, myelin-associated glycoprotein (MAG), has also been shown to protect neurons from axonal degeneration through activation of the small GTPase protein RhoA. Recent in vitro studies have shown that collapsin response mediator protein 4 (CRMP4) interacts with RhoA and that the CRMP4b/RhoA complex mediates MAG-induced inhibitory signaling against axonal outgrowth. However, whether CRMP4 is involved in MAG-mediated axon protection signaling remains unclear. Here, we show involvement of CRMP4 in MAG-induced inhibition of axonal outgrowth and axonal protection using the CRMP4-/- mouse model. In dorsal root ganglion (DRG) neurons, loss of CRMP4 prevents MAG-induced inhibition of axonal outgrowth and growth cone collapse and increases sensitivity to microtubule destabilizing factor Vincristine (VNC)-induced axonal degeneration. MAG-mediated axon protection against VNC is suppressed in CRMP4-/- DRG neurons. Understanding the molecular mechanism of MAG-mediated inhibition and protection via CRMP4 may provide novel opportunities to control axonal degeneration and regeneration.
authors.affiliation: Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nagai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D006867:Hydrolases; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D009433:Neural Inhibition; D012183:Retrograde Degeneration / Q000139:chemically induced* / Q000378:metabolism*; D015398:Signal Transduction; D050257:Tubulin Modulators; D014750:Vincristine
chemical_list: D008869:Microtubule-Associated Proteins; D018992:Myelin-Associated Glycoprotein; D050257:Tubulin Modulators; D014750:Vincristine; C501733:Dpysl5 protein, mouse; D006867:Hydrolases; D000581:Amidohydrolases