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Liberty Fran├žois-Moutal, Erik T Dustrude, Yue Wang, Tatiana Brustovetsky, Angie Dorame, Weina Ju, Aubin Moutal, Samantha Perez-Miller, Nickolay Brustovetsky, Vijay Gokhale, May Khanna, Rajesh Khanna
We previously reported that destruction of the small ubiquitin-like modifier (SUMO) modification site in the axonal collapsin response mediator protein 2 (CRMP2) was sufficient to selectively decrease trafficking of the voltage-gated sodium channel NaV1.7 and reverse neuropathic pain. Here, we further interrogate the biophysical nature of the interaction between CRMP2 and the SUMOylation machinery, and test the hypothesis that a rationally designed CRMP2 SUMOylation motif (CSM) peptide can interrupt E2 SUMO-conjugating enzyme Ubc9-dependent modification of CRMP2 leading to a similar suppression of NaV1...
October 2018: Pain
Jun Nagai, Yoshiteru Kitamura, Kazuki Owada, Naoya Yamashita, Kohtaro Takei, Yoshio Goshima, Toshio Ohshima
Axonal outgrowth inhibitors and scar formation are two major obstacles to central nervous system (CNS) repair. No target molecule that regulates both axonal growth and scarring has been identified. Here we identified collapsin response mediator protein 4 (CRMP4), a common mediator of inhibitory signals after neural injury, as a crucial factor that contributes to both axonal growth inhibition and scarring after spinal cord injury (SCI). We found increases in the inhibitory and toxic forms of CRMP4 in injured spinal cord...
February 5, 2015: Scientific Reports
Mohamad R Khazaei, Marie-Pier Girouard, Ricardo Alchini, Stephan Ong Tone, Tadayuki Shimada, Susanne Bechstedt, Mitra Cowan, Dominique Guillet, Paul W Wiseman, Gary Brouhard, Jean Francois Cloutier, Alyson E Fournier
Coordinated control of the growth cone cytoskeleton underlies axon extension and guidance. Members of the collapsin response mediator protein (CRMP) family of cytosolic phosphoproteins regulate the microtubule and actin cytoskeleton, but their roles in regulating growth cone dynamics remain largely unexplored. Here, we examine how CRMP4 regulates the growth cone cytoskeleton. Hippocampal neurons from CRMP4-/- mice exhibited a selective decrease in axon extension and reduced growth cone area, whereas overexpression of CRMP4 enhanced the formation and length of growth cone filopodia...
October 24, 2014: Journal of Biological Chemistry
Mohammad R Khazaei, Samuel Montcalm, Adriana Di Polo, Alyson E Fournier, Yves Durocher, Stephan Ong Tone
Neurons fail to re-extend their processes within the central nervous system environment in vivo, and this is partly because of inhibitory proteins expressed within myelin debris and reactive astrocytes that actively signal to the injured nerve cells to limit their growth. The ability of the trans-acting activator of transcription (TAT) protein transduction domain (PTD) to transport macromolecules across biological membranes raises the possibility of developing it as a therapeutic delivery tool for nerve regeneration...
February 2015: Journal of Molecular Neuroscience: MN
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