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Alpha 7 nicotinic receptor coupling to heterotrimeric G proteins modulates RhoA activation, cytoskeletal motility, and structural growth
Author(s) -
King Justin R.,
Kabbani Nadine
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13660
Subject(s) - rhoa , heterotrimeric g protein , microbiology and biotechnology , neurite , g protein , biology , growth cone , cytoskeleton , chemistry , signal transduction , biochemistry , axon , cell , in vitro
Nicotinic acetylcholine receptors ( nAChR s) modulate the growth and structure of neurons throughout the nervous system. Ligand stimulation of the α7 nAChR has been shown to regulate the large heterotrimeric GTP ‐binding protein (G protein) signaling in various types of cells. Here, we demonstrate a role for α7 nAChR /G protein interaction in the activation of the small (monomeric) RhoA GTP ase leading to cytoskeletal changes during neurite growth. Treatment of PC 12 cells with the α7 nAChR agonist choline or PNU ‐282987 was associated with an increase in RhoA activity and an inhibition in neurite growth. Specifically, choline treatment was found to attenuate the velocity of microtubule growth at the growth cone and decrease the rate of actin polymerization throughout the cell. The effects of α7 nAChR activation were abolished by expression of a dominant negative α7 nAChR (α7 345–348A ) deficient in G protein coupling. Proteomic analysis of immunoprecipitated α7 nAChR complexes from differentiating PC 12 cells and synaptic fractions of the developing mouse hippocampus revealed the existence of Rho GTP ase‐regulating guanine nucleotide exchange factors within α7 nAChR interactomes. These findings underscore the role of α7 nAChR /G protein in cytoskeletal regulation during neurite growth.This image depicts the hypothesized interaction of the traditionally ionotropic α7 nicotinic acetylcholine receptor (α7 nAChR ) and its ability to interact and signal through both large and small G proteins, leading to the regulation of cytoskeletal growth. Using differentiated PC 12 cells, and the specific agonist choline, it was shown that α7 nAChR /G protein interactions mediate both short‐ and long‐term neurite growth dynamics through increased RhoA activation. Activation of RhoA was shown to decrease actin polymerization, and lead to an overall decrease in neurite growth via regulation of the microtubule network. Cover Image for this issue: doi: 10.1111/jnc.13330 .