Binding of synGAP to PDZ Domains of PSD-95 is Regulated by Phosphorylation and Shapes the Composition of the Postsynaptic Density
Abstract 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 (<jats:underline>P</jats:underline>SD-95,<jats:underline>D</jats:underline>iscs-large,<jats:underline>Z</jats:underline>O-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..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 01. Juli Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Walkup, Ward G. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/058016 |
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| funding: |
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| 520 | |a Abstract 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 (<jats:underline>P</jats:underline>SD-95,<jats:underline>D</jats:underline>iscs-large,<jats:underline>Z</jats:underline>O-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. | ||
| 700 | 1 | |a Mastro, Tara |e verfasserin |4 aut | |
| 700 | 1 | |a Schenker, Leslie T. |e verfasserin |4 aut | |
| 700 | 1 | |a Vielmetter, Jost |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Iancu, Ariella |e verfasserin |4 aut | |
| 700 | 1 | |a Reghunathan, Meera |e verfasserin |4 aut | |
| 700 | 1 | |a Bannon, B. Dylan |e verfasserin |4 aut | |
| 700 | 1 | |a Mary, B. Kennedy |e verfasserin |4 aut | |
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