Wnt-7a induces presynaptic colocalization of alpha7-nicotinic acetylcholine receptors and adenomatous polyposis coli in hippocampal neurons

FARIAS, G.G.; VALLES, A.S.; COLOMBRES, M.; GODOY, J.A.; TOLEDO, E.M.; LUKAS, R.J.; BARRANTES, F.J.; INESTROSA, N.C.

JOURNAL OF NEUROSCIENCE

Society for Neuroscience

Año: 2007 vol. 27 p. 5313 - 5325

Nicotinic acetylcholine receptors (nAChRs) contribute significantly to hippocampal function.a7-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-7a, a ligand active in the canonical Wnt signaling pathway, induces dissociation of the adenomatous polyposis coli (APC) protein from the â-catenin cytoplasmic complex and the interaction of APC with a7-nAChRs in hippocampal neurons. Interestingly, Wnt-7a induces the relocalization of APC to membranes, clustering of APC in neurites, and coclustering of APC with different, presynaptic protein markers. Wnt-7a also increases the number and size of coclusters of a7-nAChRs and APC in presynaptic terminals. These short-term changes in a7-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-7a increases nAChR a7 subunit levels in an APC-independent manner and increases clusters of a7-nAChRs in neurites via an APC-dependent process. Together, these results demonstrate that stimulation through the canonical Wntpathway regulates the presynaptic localization ofAPC and a7-nAChRs with APC serving as an intermediary in the a7-nAChR relocalization process. Modulation by Wnt signaling may be essential for a7-nAChR expression and function in synapses.