A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the post synaptic density

被引：57

作者：

Walkup, Ward G. ^{[1
]}

Mastro, Tara L. ^{[1
]}

Schenker, Leslie T. ^{[1
]}

Vielmetter, Jost ^{[2
]}

Hu, Rebecca ^{[1
]}

Iancu, Ariella ^{[1
]}

Reghunathan, Meera ^{[1
]}

Bannon, Barry Dylan ^{[1
]}

Kennedy, Mary B. ^{[1
]}

机构：

[1] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[2] CALTECH, Beckman Inst, Prot Express Ctr, Pasadena, CA 91125 USA

来源：

ELIFE | 2016年 / 5卷

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

GTPASE-ACTIVATING PROTEIN; AMPA RECEPTOR TRAFFICKING; POSTSYNAPTIC DENSITY; EXCITATORY SYNAPSES; CALMODULIN-BINDING; NMDA RECEPTOR; KINASE-II; INHIBITORY SYNAPSES; SYNGAP; PLASTICITY;

D O I：

10.7554/eLife.16813

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its alpha 1 isoform binds to all three PDZ (PSD-95 Discs-large ZO-1) domains of PSD-95 the principal PSD scaffold and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-alpha 1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold which would free PDZ domains for occupancy by other proteins. Finally we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP.

引用

页数：31

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