Post-translational modification biology of glutamate receptors and drug addiction

Li Min Mao, Ming Lei Guo, Dao Zhong Jin, Eugene E. Fibuch, Eun Sang Choe, John Q. Wang

Research output: Contribution to journalReview articlepeer-review

41 Scopus citations


Post-translational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues in their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling, and protein- protein interactions), subcellular redistribution (trafficking, endocytosis, synaptic delivery, and clustering), and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamine). Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drugseeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.

Original languageEnglish (US)
Pages (from-to)4
Number of pages1
JournalFrontiers in Neuroanatomy
Issue numberMARCH
StatePublished - 2011
Externally publishedYes


  • AMPA
  • Dopamine
  • NMDA
  • Palmitoylation
  • Phosphorylation
  • Sumoylation
  • Ubiquitination
  • mGluR

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience (miscellaneous)
  • Cellular and Molecular Neuroscience


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