Downregulation of Src-kinase and glutamate-receptor phosphorylation after traumatic brain injury

Yujung Park, Tianfei Luo, Fan Zhang, Chunli Liu, Helen M. Bramlett, W. Dalton Dietrich, Bingren Hu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Phosphorylation of N-methyl-D-aspartate (NMDA) receptors is a major regulatory mechanism underlying synaptic plasticity. However, changes in NMDA receptors and phosphorylation after traumatic brain injury (TBI) remain incompletely understood. Using an animal TBI model, we observed that the protein level of NMDA receptor subunit NR2B was downregulated in synaptosomal fractions obtained from the ipsilateral neocortical injury region, whereas the levels of NR2A, NR1, and PSD93 were not significantly altered at 4 and 24 hours after TBI. Further investigation showed that tyrosine phosphorylations of NR2B Y1472 and PSD93 Y340 in synaptosomal fractions were significantly decreased relative to their total protein level after TBI. Correspondingly, phosphorylation of the Src-kinase-inhibitory site Y527 was increased, whereas phosphorylation of the activation site Y416 was decreased, indicating that the activity of Src kinase is significantly inhibited after TBI. In comparison, other Src family kinase substrates of NMDA receptor, NR2A Y1246, NR2A Y1325, and NR2B Y1070 were not obviously affected after TBI. The results suggest that TBI downregulates the Src-kinase-mediated phosphorylation of NR2 and PSD93 to destabilize the synaptic localization of NMDA receptors. Therefore, post-TBI loss of NMDA receptors may contribute to the depression of synaptic activity after TBI.

Original languageEnglish (US)
Pages (from-to)1642-1649
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2013

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Keywords

  • NMDA receptor
  • PSD93
  • Src family kinases
  • traumatic brain injury
  • tyrosine phosphorylation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

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