Synaptic PDZ domain-mediated protein interactions are disrupted by inhalational anesthetics

Ming Fang, Yuan Xiang Tao, Fahu He, Mingjie Zhang, Claire F. Levine, Peizhong Mao, Feng Tao, Chih Ling Chou, Scheherazade Sadegh-Nasseri, Roger A. Johns

Research output: Contribution to journalArticlepeer-review

Abstract

Anesthetics exert multiple effects on the central nervous system through altering synaptic transmission, but the mechanisms for this process are poorly understood. PDZ domain-mediated protein interactions play a central role in organizing signaling complexes around synaptic receptors for efficient signal transduction. We report here that clinically relevant concentrations of inhalational anesthetics dose-dependently and specifically inhibit the PDZ domain-mediated protein interaction between PSD-95 or PSD-93 and the N-methyl-D-aspartate receptor or neuronal nitric-oxide synthase. These inhibitory effects are immediate, potent, and reversible and occur at a hydrophobic peptide-binding groove on the surface of the second PDZ domain of PSD-95 in a manner relevant to anesthetic action. These findings reveal the PDZ domain as a new molecular target for inhalational anesthetics.

Original languageEnglish (US)
Pages (from-to)36669-36675
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number38
DOIs
StatePublished - Sep 19 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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