Wnt-7a induces presynaptic colocalization of alpha 7-nicotinic acetylcholine receptors and adenomatous polyposis coli in hippocampal neurons.
Nicotinic acetylcholine receptors (nAChRs) contribute significantly to hippocampal function. Alpha7-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 beta-catenin cytoplasmic complex and the interaction of APC with alpha7-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 alpha7-nAChRs and APC in presynaptic terminals. These short-term changes in alpha7-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 alpha7 subunit levels in an APC-independent manner and increases clusters of alpha7-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 alpha7-nAChRs with APC serving as an intermediary in the alpha7-nAChR relocalization process. Modulation by Wnt signaling may be essential for alpha7-nAChR expression and function in synapses.
Farías
Ginny G
GG
Centro de Regulación Celular y Patología Joaquin V. Luco, Millennium Institute for Fundamental and Applied Biology, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331010 Santiago, Chile.
Vallés
Ana S
AS
Colombres
Marcela
M
Godoy
Juan A
JA
Toledo
Enrique M
EM
Lukas
Ronald J
RJ
Barrantes
Francisco J
FJ
Inestrosa
Nibaldo C
NC
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor; D051176:beta Catenin / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D011518:Proto-Oncogene Proteins; D011978:Receptors, Nicotinic; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; C490507:Wnt7a protein, rat; D064569:alpha7 Nicotinic Acetylcholine Receptor; D051176:beta Catenin