Unknown

Dataset Information

0

A model for regulation by SynGAP-?1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density.

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

SUBMITTER: Walkup WG 

PROVIDER: S-EPMC5040590 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

Walkup Ward G WG   Mastro Tara L TL   Schenker Leslie T LT   Vielmetter Jost J   Hu Rebecca R   Iancu Ariella A   Reghunathan Meera M   Bannon Barry Dylan BD   Kennedy Mary B MB  

eLife 20160913

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<sup>2+</sup>/calmodulin-dependent pr  ...[more]

Similar Datasets

Unknown The Dual PDZ Domain from Postsynaptic Density Protein 95 Forms a Scaffold with Peptide Ligand.
| S-EPMC7399497 | biostudies-literature
Unknown A sex difference in the response of the rodent postsynaptic density to synGAP haploinsufficiency.
| S-EPMC6994236 | biostudies-literature
Unknown PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
| S-EPMC3653948 | biostudies-literature
Unknown LTP requires postsynaptic PDZ-domain interactions with glutamate receptor/auxiliary protein complexes.
| S-EPMC5899490 | biostudies-literature
Unknown Ontogeny of postsynaptic density proteins at glutamatergic synapses.
| S-EPMC1414063 | biostudies-literature
Unknown Proline-rich synapse-associated protein-1/cortactin binding protein 1 (ProSAP1/CortBP1) is a PDZ-domain protein highly enriched in the postsynaptic density.
| S-EPMC6782800 | biostudies-literature
Unknown Nanoscale scaffolding domains within the postsynaptic density concentrate synaptic AMPA receptors.
| S-EPMC3668352 | biostudies-literature
Unknown SynGAP isoforms exert opposing effects on synaptic strength.
| S-EPMC3621422 | biostudies-literature
Unknown Role of Palmitoylation of Postsynaptic Proteins in Promoting Synaptic Plasticity.
| S-EPMC6365469 | biostudies-literature
Unknown A molecular-properties-based approach to understanding PDZ domain proteins and PDZ ligands.
| S-EPMC1524865 | biostudies-literature