Roles of Synaptic MAGUK Proteins in Analgesia and Anesthesia

摘要

In the central nervous system, synapses, highly specialized sites of contact between neurons, are organized to facilitate the transmission of signals from the pre-synaptic terminal to the postsynaptic membrane and to activate subsequent signal transduction cascades that result in appropriate cellular events. Efficient and precise organization of synaptic proteins such as receptors, ion channels, and signaling molecules at both pre-synaptic and postsynaptic membranes is critical for proper signal transmission. Over the last several years, studies have revealed a much more complicated picture of ion channel mediated synaptic transmission than previously anticipated. For efficient synaptic transmission, the receptors, ion channels and their downstream signaling proteins are clustered or anchored at neuronal synapses. One family of membrane-associated guanylate kinase (MAGUK) proteins enriched in the postsynaptic density has recently been found to play a major role in the organization of receptors and related signal proteins. Neuronal MAGUK proteins include PSD-95/SAP90, PSD-93/chapsyn-110, SAP-97/hdlg, and SAP102. These four proteins have a similar structure of three tandem PDZ domains at the N-terminal side, an Src homology region 3 domain in the middle and a guanylate kinase-like domain at the C-terminal end. Via the PDZ domain-mediated protein interaction, MAGUK proteins govern many critical physiological and pathological processes in nervous system. Here, I outline our recent novel findings regarding the roles of MAGUK proteins (especial PSD-95 and PSD-93) in analgesia and anesthesia.