Wnt-7a induces presynaptic colocalization of α7-nicotinic acetylcholine receptors and adenomatous polyposis coli in hippocampal neurons

Nicotinic acetylcholine receptors (nAChRs) contribute significantly to hippocampal function. alpha 7-nAChRs are present in presynaptic sites in hippocampal neurons and may influence transmitter release, but the factors that determine their presynaptic localization are unknown. We report here that Wnt-7 alpha, a ligand active in the canonical Wnt signaling pathway, induces dissociation of the adenomatous polyposis coli (APC) protein from the beta-catenin cytoplasmic complex and the interaction of APC with alpha 7-nAChRs in hippocampal neurons. Interestingly, Wnt-7 alpha induces the relocalization of APC to membranes, clustering of APC in neurites, and coclustering of APC with different, presynaptic protein markers. Wnt-7 alpha also increases the number and size of coclusters of alpha 7-nAChRs and APC in presynaptic terminals. These short-term changes in alpha 7-nAChRs occur in the few minutes after ligand exposure and involve translocation to the plasma membrane without affecting total receptor levels. Longer-term exposure to Wnt-7 alpha increases nAChR alpha 7 subunit levels in an APC-independent manner and increases clusters of alpha 7-nAChRs in neurites via an APC-dependent process. Together, these results demonstrate that stimulation through the canonical Wnt pathway regulates the presynaptic localization of APC and alpha 7-nAChRs with APC serving as an intermediary in the alpha 7-nAChR relocalization process. Modulation by Wnt signaling may be essential for alpha 7-nAChR expression and function in synapses.