@article {Walkup058016, author = {Ward G. Walkup, 4th and Tara Mastro and Leslie T. Schenker and Jost Vielmetter and Rebecca Hu and Ariella Iancu and Meera Reghunathan and B. Dylan Bannon and B. Kennedy Mary}, title = {Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density}, elocation-id = {058016}, year = {2016}, doi = {10.1101/058016}, publisher = {Cold Spring Harbor Laboratory}, 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 Ca2+/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{\textquoteright}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.}, URL = {https://www.biorxiv.org/content/early/2016/06/09/058016}, eprint = {https://www.biorxiv.org/content/early/2016/06/09/058016.full.pdf}, journal = {bioRxiv} }