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Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal neurons by Gprin1 regulates growth
Authors:Jacob C. Nordman  Wiktor S. Phillips  Nathan Kodama  Sarah G. Clark  Christopher A. Del Negro  Nadine Kabbani
Affiliation:1. Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, , Fairfax, Virginia, USA;2. Systems Neuroscience Laboratory, Department of Applied Science, The College of William & Mary, , Williamsburg, Virginia, USA
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.
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Keywords:axon growth  choline  cytoskeleton  G protein‐regulated inducer of neurite outgrowth  hippocampus  synaptic maturation
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