A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density
- California Institute of Technology, United States
Abstract
SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP.
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Author details
Funding
National Science Foundation (2006019582)
- Ward G Walkup
National Institutes of Health (NRSA T32 GM07616)
- Ward G Walkup
Gordon and Betty Moore Foundation (Center for Integrative Study of Cell Regulation)
- Mary B Kennedy
Hicks Foundation
- Mary B Kennedy
Allen and Lenabelle Davis Foundation (Endowed Chair)
- Mary B Kennedy
National Institutes of Health (MH095095)
- Mary B Kennedy
The Beckman Institute (Protein Expression Center)
- Jost Vielmetter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (#1034-15G) of the California Institute of Technology.
Copyright
© 2016, Walkup et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density
eLife 5:e16813.
https://doi.org/10.7554/eLife.16813
