title: Collapsin response mediator protein 4 regulates growth cone dynamics through the actin and microtubule cytoskeleton.
abstract: 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. Biochemically, CRMP4 can impact both microtubule assembly and F-actin bundling in vitro. Through a structure function analysis of CRMP4, we found that the effects of CRMP4 on axon growth and growth cone morphology were dependent on microtubule assembly, whereas filopodial extension relied on actin bundling. Intriguingly, anterograde movement of EB3 comets, which track microtubule protrusion, slowed significantly in neurons derived from CRMP4-/- mice, and rescue of microtubule dynamics required CRMP4 activity toward both the actin and microtubule cytoskeleton. Together, this study identified a dual role for CRMP4 in regulating the actin and microtubule growth cone cytoskeleton.
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, 3801 Rue University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Mohamad R
authors.initials: MR
authors.lastname: Khazaei
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, 3801 Rue University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Marie-Pier
authors.initials: MP
authors.lastname: Girouard
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, 3801 Rue University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Alchini
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, 3801 Rue University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ong Tone
authors.affiliation: Neural Plasticity Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Biology, McGill University, Montréal H3G 0B1, Canada.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bechstedt
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal H2X 0A9, Canada.
authors.forename: Mitra
authors.initials: M
authors.lastname: Cowan
authors.affiliation: Department of Physics, McGill University, Montréal H3A 2T8, Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guillet
authors.affiliation: Department of Physics, McGill University, Montréal H3A 2T8, Canada, Department of Chemistry, McGill University, Montréal H3A 2K6, Canada, and.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Wiseman
authors.affiliation: Department of Biology, McGill University, Montréal H3G 0B1, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Brouhard
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, 3801 Rue University, Montréal, Québec H3A 2B4, Canada.
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Cloutier
authors.affiliation: From the Department of Neurology and Neurosurgery, Montréal Neurological Institute, 3801 Rue University, Montréal, Québec H3A 2B4, Canada, alyson.fournier@mcgill.ca.
authors.forename: Alyson E
authors.initials: AE
authors.lastname: Fournier
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D048429:Cell Size; D005260:Female; D020439:Growth Cones / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000378:metabolism
chemical_list: C526904:Dpysl3 protein, mouse; C522423:EB3 protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin
keywords: Axon; CRMP; Cell Biology; Cytoskeleton; Growth Cone; Microfilaments; Microtubule; Neurodevelopment; Neuroscience