Identification of CRMP4 as a Convergent Regulator of Axon Outgrowth Inhibition

• DOI: 10.1523/jneurosci.5055-06.2007
• Publication Date: 2007-02-14T16:35:10Z
• Authors: Yazan Z. Alabed; Madeline Pool; Stephan Ong Tone; Alyson E. Fournier
• Keywords: Neurite; Growth cone; Small GTPase; Rac GTP-Binding Proteins; Chondroitin sulfate proteoglycan

Myelin-associated inhibitors (MAIs) and chondroitin sulfate proteoglycans (CSPGs) contribute to failed regeneration after neuronal injury. MAIs CSPGs stimulate intracellular signals including the activation of RhoA Rho kinase block axonal extension through targeted modifications cytoskeleton. ROCK are promising targets for therapeutic intervention promote CNS repair; however, their ubiquitous expression will limit specificity drugs these molecules. We have identified cytosolic phosphoprotein CRMP4b (collapsin-response mediator protein 4b) as a that physically functionally interacts with mediate neurite outgrowth inhibition. Short interfering RNA-mediated knockdown CRMP4 promotes on myelin substrates, indicating critical role in Disruption CRMP4b–RhoA binding competitive inhibitor attenuates inhibition aggrecan substrates. Stimulation growth cones Nogo leads colocalization at discrete regions within actin-rich central peripheral domains cone, indicative potential function cytoskeletal rearrangements during Together, data indicate RhoA–CRMP4b complex forms response inhibitory challenges cone environment regulates dynamics distinct sites necessary axon Competitive suggests novel, highly specific avenue promoting