Autor: |
Rebecca Hu, B. Dylan Bannon, Ward G. Walkup, Tara L Mastro, Ariella Iancu, Mary B. Kennedy, Jost Vielmetter, Leslie T. Schenker, Meera Reghunathan |
Rok vydání: |
2016 |
Předmět: |
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Popis: |
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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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