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The Journal of Neuroscience, May 16, 2007, 27(20):5313-5325; doi:10.1523/JNEUROSCI.3934-06.2007

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Cellular/Molecular
Wnt-7a Induces Presynaptic Colocalization of {alpha}7-Nicotinic Acetylcholine Receptors and Adenomatous Polyposis Coli in Hippocampal Neurons

Ginny G. Farías,1 Ana S. Vallés,2 Marcela Colombres,1 Juan A. Godoy,1 Enrique M. Toledo,1 Ronald J. Lukas,3 Francisco J. Barrantes,2 and Nibaldo C. Inestrosa1

1Centro 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, 2Instituto de Investigaciones Bioquímicas de Bahía Blanca, 8000 Bahía Blanca, Argentina, and 3Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona 85013

Correspondence should be addressed to Dr. Nibaldo C. Inestrosa, Centro de Regulación Celular y Patología "Joaquin V. Luco" Biomedical Center, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago, Chile. Email: ninestr{at}bio.puc.cl

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-7a, a ligand active in the canonical Wnt signaling pathway, induces dissociation of the adenomatous polyposis coli (APC) protein from the ß-catenin cytoplasmic complex and the interaction of APC with {alpha}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 {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-7a 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.

Key words: nAChR; APC; synapse; Wnt; Wnt target gene; neurons

Received May 2, 2006; revised March 19, 2007; accepted March 24, 2007.

Correspondence should be addressed to Dr. Nibaldo C. Inestrosa, Centro de Regulación Celular y Patología "Joaquin V. Luco" Biomedical Center, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago, Chile. Email: ninestr{at}bio.puc.cl




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W. Cerpa, J. A. Godoy, I. Alfaro, G. G. Farias, M. J. Metcalfe, R. Fuentealba, C. Bonansco, and N. C. Inestrosa
Wnt-7a Modulates the Synaptic Vesicle Cycle and Synaptic Transmission in Hippocampal Neurons
J. Biol. Chem., February 29, 2008; 283(9): 5918 - 5927.
[Abstract] [Full Text] [PDF]


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