title: Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors.
abstract: The dendritic targeting of neurotransmitter receptors is vital for dendritic development and function. However, how such localization is established remains unclear. Here we show that semaphorin 3A (Sema3A) signalling at the axonal growth cone is propagated towards the cell body by retrograde axonal transport and drives AMPA receptor GluA2 to the distal dendrites, which regulates dendritic development. Sema3A enhances glutamate receptor interacting protein 1-dependent localization of GluA2 in dendrites, which is blocked by knockdown of cytoplasmic dynein heavy chain. PlexinA (PlexA), a receptor component for Sema3A, interacts with GluA2 at the immunoglobulin-like Plexin-transcription-factor domain (PlexA-IPT) in somatodendritic regions. Overexpression of PlexA-IPT suppresses dendritic localization of GluA2 and induces aproximal bifurcation phenotype in the apical dendrites of CA1 hippocampal neurons. Thus, we propose a control mechanism by which retrograde Sema3A signalling regulates the glutamate receptor localization through trafficking of cis-interacting PlexA with GluA2 along dendrites.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, 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, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Usui
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Sandy
authors.initials: S
authors.lastname: Chen
authors.affiliation: 1] Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan [2].
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hida
authors.affiliation: National Center of Neurology and Psychiatry, National Institute of Neuroscience, Department of Ultrastructural Research, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Suto
authors.affiliation: Research Institute for Frontier Medicine, Department of Cell Science, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: 1] Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan [2] CREST, Japan Science and Technology Agency, 4-1-8 Hontyou, Kawaguchi 332-0012, Japan [3].
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Takei
authors.affiliation: 1] Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan [2] CREST, Japan Science and Technology Agency, 4-1-8 Hontyou, Kawaguchi 332-0012, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000196:embryology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D002352:Carrier Proteins; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C575033:Plxna4 protein, rat; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; D049452:Green Fluorescent Proteins; C104722:glutamate receptor ionotropic, AMPA 2