Shank Modulates Postsynaptic Wnt Signaling to Regulate Synaptic Development
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5820.full.pdf
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Author(s)
Akbergenova, Yulia
Cho, Richard W.
Baas-Thomas, Maximilien S.
Littleton, J. Troy
Harris, Kathryn P.
Date Issued
May 2016
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Harris, K. P., et al. “Shank Modulates Postsynaptic Wnt Signaling to Regulate Synaptic Development.” Journal of Neuroscience, vol. 36, no. 21, May 2016, pp. 5820–32. © 2016 the Authors
Version
Final published version
Abstract
Prosap/Shank scaffolding proteins regulate the formation, organization, and plasticity of excitatory synapses. Mutations in SHANK family genes are implicated in autism spectrum disorder and other neuropsychiatric conditions. However, the molecular mechanisms underlying Shank function are not fully understood, and no study to date has examined the consequences of complete loss of all Shank proteins in vivo. Here we characterize the single Drosophila Prosap/Shank family homolog. Shank is enriched at the postsynaptic membrane of glutamatergic neuromuscular junctions and controls multiple parameters of synapse biology in a dose-dependent manner. Both loss and overexpression of Shank result in defects in synaptic bouton number and maturation. We find that Shank regulates a noncanonical Wnt signaling pathway in the postsynaptic cell by modulating the internalization of the Wnt receptor Fz2. This study identifies Shank as a key component of synaptic Wnt signaling, defining a novel mechanism for how Shank contributes to synapse maturation during neuronal development.Keywords: postsynaptic scaffold, Shank, synaptic development, Wnt signaling
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1523/JNEUROSCI.4279-15.2016
