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bioRxiv · 10.1101/058016

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
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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 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'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.

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Ward G Walkup, Tara L Mastro, Leslie T Schenker, Jost Vielmetter, Rebecca Hu, Ariella Iancu, Meera Reghunathan, Barry D Bannon, Mary B Kennedy. 2016-06-09. Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density. https://doi.org/10.1101/058016

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