title: An interaction between α7 nicotinic receptors and a G-protein pathway complex regulates neurite growth in neural cells.
abstract: The α7 acetylcholine nicotinic receptor (α7) is an important mediator of cholinergic transmission during brain development. Here we present an intracellular signaling mechanism for the α7 receptor. Proteomic analysis of immunoprecipitated α7 subunits reveals an interaction with a G protein pathway complex (GPC) comprising Gα(i/o), GAP-43 and G protein regulated inducer of neurite outgrowth 1 (Gprin1) in differentiating cells. Morphological studies indicate that α7 receptors regulate neurite length and complexity via a Gprin1-dependent mechanism that directs the expression of α7 to the cell surface. α7-GPC interactions were confirmed in embryonic cortical neurons and were found to modulate the growth of axons. Taken together, these findings reveal a novel intracellular pathway of signaling for α7 within neurons, and suggest a role for its interactions with the GPC in brain development.
authors.affiliation: Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia 22030,  USA.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Nordman
authors.forename: Nadine
authors.initials: N
authors.lastname: Kabbani
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002038:Bungarotoxins / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D019922:GAP-43 Protein / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002038:Bungarotoxins; D002147:Calmodulin; C579165:Chrna7 protein, rat; D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go