PSD-93 Interacts with SynGAP and Promotes SynGAP Ubiquitination and Ischemic Brain Injury in Mice.

Translational Stroke Research
Qingxiu ZhangLiangqun Rong

Abstract

Postsynaptic density protein-93 (PSD-93) plays an important role in ischemic brain injury through N-methyl-D-aspartate receptor (NMDAR)-triggered neurotoxicity. GTPase-activating protein for Ras (SynGAP) is a GAP specifically expressed in the central nervous system to regulate nerve development and synaptic plasticity. However, the link between PSD-93 and SynGAP and their role in ischemic brain injury remain elusive. Here, we showed that PSD-93 interacted with SynGAP and mediated SynGAP ubiquitination and degradation following ischemic brain injury. Proteasome inhibitor MG-132 could reverse the decrease of SynGAP protein level in wild-type mice following cerebral ischemia reperfusion through inhibiting SynGAP ubiquitination. Furthermore, NMDA receptor inhibitor MK801 could increase SynGAP protein level in wild-type mice following cerebral ischemia reperfusion. However, in PSD-93 knockout mice, MG-132 or NMDAR inhibitor had no significant effect on SynGAP expression. Both MG-132 and PSD-93 knockout reduced infarct volume and improved neurological deficit in mice at different time points after cerebral ischemia reperfusion. Furthermore, we identified that 670-685 amino acid sequence of SynGAP was essential to the binding of SynGA...Continue Reading

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Citations

Feb 23, 2021·Frontiers in Synaptic Neuroscience·Abhishek SahasrabudheDeanna L Benson
Oct 29, 2021·Translational Stroke Research·Hidenori SuzukiMasashi Fujimoto

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Methods Mentioned

BETA
ubiquitination
PCR
electrophoresis
Co-immunoprecipitation

Software Mentioned

ImagePro Plus
SPSS
Primer Express

Related Concepts

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