Wnt-7A Induces Presynaptic Colocalization Of Î±7-Nicotinic Acetylcholine Receptors And Adenomatous Polyposis Coli In Hippocampal Neurons
Nicotinic acetylcholine receptors (nAChRs) contribute significantly to hippocampal function. Î±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-7a, a ligand active in the canonical Wnt signaling pathway, induces dissociation of the adenomatous polyposis coli (APC) protein from the Î²-catenin cytoplasmic complex and the interaction of APC with Î±7-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 Î±7-nAChRs and APC in presynaptic terminals. These short-term changes in Î±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-7a increases nAChR Î±7 subunit levels in an APC-independent manner and increases clusters of Î±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 Î±7-nAChRs with APC serving as an intermediary in the Î±7-nAChR relocalization process. Modulation by Wnt signaling may be essential for Î±7-nAChR expression and function in synapses. Copyright Â© 2007 Society for Neuroscience.
Journal of Neuroscience
Digital Object Identifier (DOI)
FarÃas, Ginny G.; VallÃ©s, Ana S.; Colombres, Marcela; Godoy, Juan A.; Toledo, Enrique M.; Lukas, Ronald J.; Barrantes, Francisco J.; and Inestrosa, Nibaldo C., "Wnt-7A Induces Presynaptic Colocalization Of Î±7-Nicotinic Acetylcholine Receptors And Adenomatous Polyposis Coli In Hippocampal Neurons" (2007). Neurobiology. 288.