CRMP4 mediates MAG-induced inhibition of axonal outgrowth and protection against Vincristine-induced axonal degeneration

Jun Nagai, Yoshio Goshima, Toshio Ohshima

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)56-61
    Number of pages6
    JournalNeuroscience Letters
    Volume519
    Issue number1
    DOIs
    Publication statusPublished - 2012 Jun 21

    Fingerprint

    Semaphorin-3A
    Myelin-Associated Glycoprotein
    Vincristine
    Proteins
    Spinal Ganglia
    Myelin Sheath
    Axons
    rhoA GTP-Binding Protein
    Neurons
    Nerve Degeneration
    Growth Cones
    Monomeric GTP-Binding Proteins
    Microtubules
    Regeneration

    Keywords

    • Axonal degeneration
    • Axonal outgrowth
    • Axonal regeneration
    • CRMP
    • MAG
    • Vincristine

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    CRMP4 mediates MAG-induced inhibition of axonal outgrowth and protection against Vincristine-induced axonal degeneration. / Nagai, Jun; Goshima, Yoshio; Ohshima, Toshio.

    In: Neuroscience Letters, Vol. 519, No. 1, 21.06.2012, p. 56-61.

    Research output: Contribution to journalArticle

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