title: Voltage-gated calcium and sodium channels mediate Sema3A retrograde signaling that regulates dendritic development.
abstract: Growing axons rely on local signaling at the growth cone for guidance cues. Semaphorin3A (Sema3A), a secreted repulsive axon guidance molecule, regulates synapse maturation and dendritic branching. We previously showed that local Sema3A signaling in the growth cones elicits retrograde retrograde signaling via PlexinA4 (PlexA4), one component of the Sema3A receptor, thereby regulating dendritic localization of AMPA receptor GluA2 and proper dendritic development. In present study, we found that nimodipine (voltage-gated L-type Ca(2+) channel blocker) and tetrodotoxin (TTX; voltage-gated Na(+) channel blocker) suppress Sema3A-induced dendritic localization of GluA2 and dendritic branch formation in cultured hippocampal neurons. The local application of nimodipine or TTX to distal axons suppresses retrograde transport of Venus-Sema3A that has been exogenously applied to the distal axons. Sema3A facilitates axonal transport of PlexA4, which is also suppressed in neurons treated with either TTX or nimodipine. These data suggest that voltage-gated calcium and sodium channels mediate Sema3A retrograde signaling that regulates dendritic GluA2 localization and branch formation.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA; JSPS Postdoctoral Fellowship for Research Abroad, Chiyoda-ku 102-0083, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamashita
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Aoki
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Sandy
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Jitsuki-Takahashi
authors.affiliation: Department of Neurobiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohura
authors.affiliation: Department of Neurobiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Kamiya
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: goshima@med.yokohama-cu.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D020439:Growth Cones / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D040121:Semaphorin-3A / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D018091:Receptors, AMPA; C488218:Sema3a protein, rat; D040121:Semaphorin-3A; D015222:Sodium Channels; D013779:Tetrodotoxin; D009553:Nimodipine; D002118:Calcium
keywords: Axonal transport; Dendrite; GluA2; Semaphorin3A; Voltage-gated ion channels