Nordman_2014_J.Neurochem_129_649

Cholinergic signaling plays an important role in regulating the growth and regeneration of axons in the nervous system. The alpha7 nicotinic receptor (alpha7) can drive synaptic development and plasticity in the hippocampus. Here, we show that activation of alpha7 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 alpha7 at the growth cone. In addition, an alpha7/Gprin1 interaction appears intimately linked to a Galphao, growth-associated protein 43, and CDC42 cytoskeletal regulatory pathway within the developing axon. These findings demonstrate that alpha7 regulates axon growth in hippocampal neurons, thereby likely contributing to synaptic formation in the developing brain.