Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published July 26, 2016 | Submitted
Report Open

Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density

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.

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.

Attached Files

Submitted - 058016.full.pdf

Files

058016.full.pdf
Files (15.4 MB)
Name Size Download all
md5:3bed8aad2252dbee83f05927b7b9ce30
15.4 MB Preview Download

Additional details

Created:
September 15, 2023
Modified:
October 23, 2023