RT Journal Article
SR Electronic
T1 Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 058016
DO 10.1101/058016
A1 Ward G. Walkup, 4th
A1 Tara Mastro
A1 Leslie T. Schenker
A1 Jost Vielmetter
A1 Rebecca Hu
A1 Ariella Iancu
A1 Meera Reghunathan
A1 B. Dylan Bannon
A1 B. Kennedy Mary
YR 2016
UL http://biorxiv.org/content/early/2016/06/09/058016.abstract
AB 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.