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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 ?7 nicotinic receptor (?7) can drive synaptic development and plasticity in the hippocampus. Here, we show that activation of ?7 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 ?7 at the growth cone. In addition, an ?7/Gprin1 interaction appears intimately linked to a G?o, growth-associated protein 43, and CDC42 cytoskeletal regulatory pathway within the developing axon. These findings demonstrate that ?7 regulates axon growth in hippocampal neurons, thereby likely contributing to synaptic formation in the developing brain.

SUBMITTER: Nordman JC 

PROVIDER: S-EPMC4496803 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Axon targeting of the alpha 7 nicotinic receptor in developing hippocampal neurons by Gprin1 regulates growth.

Nordman Jacob C JC   Phillips Wiktor S WS   Kodama Nathan N   Clark Sarah G SG   Del Negro Christopher A CA   Kabbani Nadine N  

Journal of neurochemistry 20140110 4


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  ...[more]

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