title: A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling.
abstract: Semaphorin3A (Sema3A) is a secreted type of axon guidance molecule that regulates axon wiring through complexes of neuropilin-1 (NRP1) with PlexinA protein receptors. Sema3A regulates the dendritic branching through tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexA proteins and tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7 (encoded bySCN9A), a TTX-sensitive Na+channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport. In mouse dorsal root ganglion (DRG) neurons, Sema3A increased co-localization of PlexA4 and TrkA in the growth cones and axons. TTX treatment and RNAi knockdown of Nav1.7 sustained Sema3A-induced colocalized signals of PlexA4 and TrkA in growth cones and suppressed the subsequent localization of PlexA4 and TrkA in distal axons. A similar localization phenotype was observed incrmp1-/-DRG neurons. Sema3A induced colocalization of CRMP1 and Nav1.7 in the growth cones. The half maximal voltage was increased incrmp1-/-neurons when compared to that in wild type. In HEK293 cells, introduction of CRMP1 lowered the threshold of co-expressed exogenous Nav1.7. These results suggest that Nav1.7, by coupling with CRMP1, mediates the axonal retrograde signaling of Sema3A.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamane
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan goshima@med.yokohama-cu.ac.jp ynaoya-ycu@umin.net.|Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Naoya
authors.identifier: 0000-0001-7667-5264
authors.initials: N
authors.lastname: Yamashita
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.|RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Tomonobu
authors.identifier: 0000-0002-8032-7243
authors.initials: T
authors.lastname: Hida
authors.affiliation: Department of Anesthesiology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, 4132 Urasa, Minami-uonuma, Niigata 949-7302, Japan.
authors.forename: Yoshinori
authors.identifier: 0000-0001-9790-9867
authors.initials: Y
authors.lastname: Kamiya
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Fumio
authors.identifier: 0000-0003-2029-6083
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
authors.forename: Pappachan
authors.initials: P
authors.lastname: Kolattukudy
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan goshima@med.yokohama-cu.ac.jp ynaoya-ycu@umin.net.
authors.forename: Yoshio
authors.identifier: 0000-0002-1944-7051
authors.initials: Y
authors.lastname: Goshima
mesh_terms: D000818:Animals; D000071437:Axon Guidance; D005727:Ganglia, Spinal / Q000166:cytology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009415:Nerve Net; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D039942:Neuropilin-1 / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism; D040121:Semaphorin-3A / Q000378:metabolism*; D015398:Signal Transduction; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D039942:Neuropilin-1; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; C502872:Crmp1 protein, mouse; D000098855:Collapsin Response Mediator Protein 1; C492110:Plxna4 protein, mouse; C503479:Scn9a protein, mouse
keywords: Axonal transport; CRMP1; PlexA4; Semaphorin3A; TrkA; Voltage-dependent Na+ channels