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

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 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 domai...

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Bibliographic Details
Published in:eLife 2016-09, Vol.5
Main Authors: Walkup, Ward G, Mastro, Tara L, Schenker, Leslie T, Vielmetter, Jost, Hu, Rebecca, Iancu, Ariella, Reghunathan, Meera, Bannon, Barry Dylan, Kennedy, Mary B
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Ca2+/calmodulin-dependent protein kinase II
Calcium
Calcium-binding protein
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Calmodulin
CaMKII
Competition
Disks Large Homolog 4 Protein - metabolism
Forebrain
GTPase-activating protein
Guanosine triphosphatases
Immunoglobulins
Kinases
Ligands
Mice
Neural circuitry
Neuroscience
Observations
PDZ Domains
Phosphorylation
Physiological aspects
Polo-like kinase
Post-Synaptic Density - chemistry
Postsynaptic density
Postsynaptic density proteins
Protein binding
Protein Processing, Post-Translational
Protein-Serine-Threonine Kinases - metabolism
Proteins
ras GTPase-Activating Proteins - metabolism
Regulation
Rodents
Synapses
synaptic plasticity
SynGAP haploinsufficiency
Zonula occludens-1 protein
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Summary:SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 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-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca /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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.16813