Walkup, Ward G. and Mastro, Tara and Schenker, Leslie T. and Vielmetter, Jost and Hu, Rebecca and Iancu, Ariella and Reghunathan, Meera and Bannon, B. Dylan and Kennedy, Mary B. (2016) Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density. . (Submitted) https://resolver.caltech.edu/CaltechAUTHORS:20160718-135600220
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Abstract
SynGAP is a Ras/Rap GTPase-activating protein (GAP) present in high concentration in postsynaptic densities (PSDs) from mammalian forebrain where it binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95. We show that phosphorylation of synGAP by Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured by surface plasmon resonance. SynGAP is abundant enough in postsynaptic densities (PSDs) to occupy about one third of the PDZ domains of PSD-95. Therefore, we hypothesize that phosphorylation by CaMKII reduces synGAP′s ability to restrict binding of other proteins to the PDZ domains of PSD-95. We support this hypothesis by showing that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present at a higher ratio to PSD-95 in PSDs isolated from synGAP heterozygous mice.
Item Type: | Report or Paper (Discussion Paper) | ||||||||||||||||
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Additional Information: | The copyright holder for this preprint is the author/funder. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Jun. 9, 2016. This work was supported in part by grants from the Gordon and Betty Moore Foundation (Center for Integrative Study of Cell Regulation), the Hicks Foundation for Alzheimer’s Research, the Allen and Lenabelle Davis Foundation, and from National Institutes of Health Grant MH095095 to MBK. WGW IV was supported by the National Science Foundation Graduate Research Fellowship under Grant No. 62006019582, and the National Institutes of Health under Grant No. NIH/NRSA 5 T32 GM07616. The Protein Expression Center is supported by the Beckman Institute. Conflict of interest: The authors declare that they have no conflicts of interest concerning the contents of this article. | ||||||||||||||||
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Record Number: | CaltechAUTHORS:20160718-135600220 | ||||||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20160718-135600220 | ||||||||||||||||
Official Citation: | Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density Ward G Walkup, Tara L Mastro, Leslie T Schenker, Jost Vielmetter, Rebecca Hu, Ariella Iancu, Meera Reghunathan, Barry D Bannon, Mary B Kennedy bioRxiv 058016; doi: http://dx.doi.org/10.1101/058016 | ||||||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||
ID Code: | 69096 | ||||||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||||||
Deposited By: | Tony Diaz | ||||||||||||||||
Deposited On: | 26 Jul 2016 23:59 | ||||||||||||||||
Last Modified: | 03 Oct 2019 10:19 |
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