Nordman_2012_J.Cell.Sci_125_5502

The alpha7 acetylcholine nicotinic receptor (alpha7) is an important mediator of cholinergic transmission during brain development. Here we present an intracellular signaling mechanism for the alpha7 receptor. Proteomic analysis of immunoprecipitated alpha7 subunits reveals an interaction with a G protein pathway complex (GPC) comprising Galpha(i/o), GAP-43 and G protein regulated inducer of neurite outgrowth 1 (Gprin1) in differentiating cells. Morphological studies indicate that alpha7 receptors regulate neurite length and complexity via a Gprin1-dependent mechanism that directs the expression of alpha7 to the cell surface. alpha7-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 alpha7 within neurons, and suggest a role for its interactions with the GPC in brain development.