title: Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal neurons by Gprin1 regulates growth.
abstract: Cholinergic signaling plays an important role in regulating the growth and regeneration of axons in the nervous system. The α7 nicotinic receptor (α7) can drive synaptic development and plasticity in the hippocampus. Here, we show that activation of α7 significantly reduces axon growth in hippocampal neurons by coupling to G protein-regulated inducer of neurite outgrowth 1 (Gprin1), which targets it to the growth cone. Knockdown of Gprin1 expression using RNAi is found sufficient to abolish the localization and calcium signaling of α7 at the growth cone. In addition, an α7/Gprin1 interaction appears intimately linked to a Gαo, growth-associated protein 43, and CDC42 cytoskeletal regulatory pathway within the developing axon. These findings demonstrate that α7 regulates axon growth in hippocampal neurons, thereby likely contributing to synaptic formation in the developing brain.
authors.affiliation: Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia, USA.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Nordman
authors.forename: Wiktor S
authors.initials: WS
authors.lastname: Phillips
authors.forename: Nathan
authors.initials: N
authors.lastname: Kodama
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Clark
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Del Negro
authors.forename: Nadine
authors.initials: N
authors.lastname: Kabbani
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D005260:Female; D019922:GAP-43 Protein / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D025941:Protein Interaction Mapping; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014862:Wasp Venoms / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000502:physiology
chemical_list: D000109:Acetylcholine; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D002038:Bungarotoxins; D002794:Choline; D019922:GAP-43 Protein; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D037342:Pertussis Toxin; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate; D014862:Wasp Venoms; D064569:alpha7 Nicotinic Acetylcholine Receptor; D020764:cdc42 GTP-Binding Protein; C579165:Chrna7 protein, rat; C498513:PNU-282987; C037500:mastoparan
keywords: G protein-regulated inducer of neurite outgrowth; axon growth; choline; cytoskeleton; hippocampus; synaptic maturation