Synaptic PDZ domain-mediated protein interactions are disrupted by inhalational anesthetics.
- Additional Document Info
- View All
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.
complete list of authors
Fang, Ming||Tao, Yuan-Xiang||He, Fahu||Zhang, Mingjie||Levine, Claire F||Mao, Peizhong||Tao, Feng||Chou, Chih-Ling||Sadegh-Nasseri, Scheherazade||Johns, Roger A