Wnt-7a Induces Presynaptic Colocalization of α7-Nicotinic Acetylcholine Receptors and Adenomatous Polyposis Coli in Hippocampal Neurons
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Nicotinic acetylcholine receptors (nAChRs) contribute significantly to hippocampal function. α7-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 β-catenin cytoplasmic complex and the interaction of APC with α7-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 α7-nAChRs and APC in presynaptic terminals. These short-term changes in α7-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 α7 subunit levels in an APC-independent manner and increases clusters of α7-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 α7-nAChRs with APC serving as an intermediary in the α7-nAChR relocalization process. Modulation by Wnt signaling may be essential for α7-nAChR expression and function in synapses.
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Wnt2 and other proteins usually linked to neural development might also play significant roles in regulating neuronal function after critical periods.
“nonetheless, Wnt2 and other proteins traditionally associated with neural development may have important roles in post-critical period regulation of neuronal function (Farias et al., 2007; Moon et al., 2004; Wayman et al., 2006).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Farias et al., 2007
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Wnt Signaling in Neural Development
Dorsky, R. I. (2014) · doi:10.1002/9781118444122.ch21
- Authors
- Farías, G. G., Vallés, A. S., Colombres, M., Godoy, J. A., Toledo, E. M., Lukas, R. J., Barrantes, F. J., & Inestrosa, N. C.
- Affiliations
- Pontificia Universidad Católica de Chile (CL)
- Barrow Neurological Institute (US)
- Instituto de Investigaciones Bioquímicas de Bahía Blanca, CONICET-UNS (AR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-05-16
- Volume
- 27
- Issue
- 20
- Pages
- 5313-5325
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672358
- OpenAlex
- W2081376704
- Cited by
- 108
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 8 · 2013: 17 · 2012: 8
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
- Funders
- Barrow Neurological Foundation
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Universidad Nacional del Sur
- Arizona Biomedical Research Commission
- National Institutes of Health (DA015389)
- Comisión Nacional de Investigación Científica y Tecnológica
- National Institute on Drug Abuse (R01DA015389, DA015389)
- National Institute of Neurological Disorders and Stroke (NS040417, R01NS040417)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Wnt7a, alpha7 nicotinic acetylcholine receptor, adenomatous polyposis coli, presynaptic localization, hippocampal neurons, Wnt/β-catenin signaling, β-catenin, synaptic transmission, plasma membrane translocation
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Hippocampus, Humans, Mice, Inbred C57BL, Neurons, Proto-Oncogene Proteins, Receptors, Nicotinic, Signal Transduction, Rats, Sprague-Dawley, Presynaptic Terminals, Adenomatous Polyposis Coli Protein, Wnt Proteins, beta Catenin, Mice, Rats, alpha7 Nicotinic Acetylcholine Receptor
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