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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 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. 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 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 7-nAChRs and APC in presynaptic terminals. These short-term changes in 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 7 subunit levels in an APC-independent manner and increases clusters of 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 7-nAChRs with APC serving as an intermediary in the 7-nAChR relocalization process. Modulation by Wnt signaling may be essential for 7-nAChR expression and function in synapses.

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

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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

This article has been cited by other articles:

				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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