Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses
Open accessAbstract
Growing evidence indicates that Wingless-type (Wnt) signaling plays an important role in the maturation of the central nervous system. We report here that Wingless-type family member 5A (Wnt-5a) is expressed early in development and stimulates dendrite spine morphogenesis, inducing de novo formation of spines and increasing the size of the preexisting ones in hippocampal neurons. Wnt-5a increased intracellular calcium concentration in dendritic processes and the amplitude of NMDA spontaneous miniature currents. Acute application of Wnt-5a increased the amplitude of field excitatory postsynaptic potentials (fEPSP) in hippocampal slices, an effect that was prevented by calcium-channel blockers. The physiological relevance of our findings is supported by studies showing that Wnt scavengers decreased spine density, miniature excitatory postsynaptic currents, and fEPSP amplitude. We conclude that Wnt-5a stimulates different aspects of synaptic differentiation and plasticity in the mammalian central nervous system.
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Frizzled-mediated Wnt/β-catenin signaling plays an important role in synaptic plasticity.
“Frizzled-mediated Wnt/β-catenin signaling has been shown to play an important role in synaptic plasticity (Chen et al., 2006; Varela-Nallar et al., 2010; Varela-Nallar et al., 2009).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Varela-Nallar et al., 2010
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“For example, WNT5A stimulates the formation of dendrite spines and enhances synaptic plasticity in mammalian brain (Varela-Nallar et al., 2010).”
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- Authors
- Varela-Nallar, L., Alfaro, I. E., Serrano, F. G., Parodi, J., & Inestrosa, N. C.
- Affiliations
- Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
- Pontificia Universidad Católica de Chile (CL)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-17
- Volume
- 107
- Issue
- 49
- Pages
- 21164-21169
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3000271
- OpenAlex
- W2146455000
- Cited by
- 197
- References
- 45
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 13 · 2021: 10 · 2020: 12 · 2019: 6 · 2018: 11 · 2017: 12 · 2016: 15 · 2015: 16 · 2014: 27 · 2013: 27 · 2012: 15
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- Comisión Nacional de Investigación Científica y Tecnológica (79090027, PFB12/2007)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Wnt5a, Wnt signaling, synaptic differentiation, glutamatergic synapses, dendritic spine morphogenesis, hippocampal neurons, intracellular calcium, excitatory postsynaptic potentials, synaptic plasticity, central nervous system development
- MeSH terms
- Wnt-5a Protein, Animals, Cell Differentiation, Dendrites, Hippocampus, Neuronal Plasticity, Neurons, Synapses, N-Methylaspartate, Glutamic Acid, Excitatory Postsynaptic Potentials, Dendritic Spines, Wnt Proteins, Mice
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