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Transient cerebral ischemia increases tyrosine phosphorylation of the synaptic RAS-GTPase activating protein, SynGAP

L Pei1, R L Teves, M C Wallace

  • 1Center for the Neurobiology of Stress, Division of Life Sciences, University of Toronto at Scarborough, Ontario, Canada.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
|August 7, 2001
PubMed

Insights

Cerebral ischemia elevates SynGAP tyrosine phosphorylation, impacting its interactions within postsynaptic densities. These SynGAP changes may contribute to brain injury following ischemic events.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Cerebral ischemia triggers signaling pathways like MAPK and increases protein tyrosine phosphorylation at postsynaptic densities (PSDs).
  • SynGAP (postsynaptic density-95/discs large/zonula occludens-1-associated guanylate kinase), a brain-specific Ras GTPase-activating protein, is enriched in PSDs.

Purpose of the Study:

  • To investigate the relationship between cerebral ischemia and tyrosine phosphorylation of SynGAP.
  • To determine the effect of ischemia on SynGAP's interaction with other PSD proteins and its RasGAP activity.

Main Methods:

  • Transient global cerebral ischemia was induced in rats via 4-vessel occlusion.
  • Postsynaptic densities (PSDs) were isolated from rat forebrains at various reperfusion time points.
  • Tyrosine phosphorylation of SynGAP, its RasGAP activity, and its interactions with Src, Fyn, and PSD-95 were analyzed.

Main Results:

  • SynGAP tyrosine phosphorylation significantly increased after 20 minutes of reperfusion and remained elevated for 24 hours.
  • Enhanced SynGAP phosphorylation did not alter its PSD RasGAP activity.
  • Ischemia increased SynGAP binding to Src and Fyn SH2 domains but decreased its co-immunoprecipitation with PSD-95.

Conclusions:

  • Ischemia induces significant changes in SynGAP tyrosine phosphorylation and its molecular interactions within PSDs.
  • Altered SynGAP properties and interactions following ischemia may play a role in the resulting neuropathology.

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