STRUCTURE, DIVERSITY AND SYNAPTIC LOCALIZATION OF INHIBITORY GLYCINE RECEPTORS

The inhibitory glycine receptor (GlyR) mediates postsynaptic inhibitio n in spinal cord, brain stem and other regions of the vertebrate centr al nervous system. Biochemical and molecular approaches have identifie d different developmentally and regionally regulated GlyR isoforms tha t result from the differential expression of at least four genes codin g for different variants of the ligand-binding alpha subunit. Molecula r studies have allowed identification of GlyR subunit domains implicat ed in ligand binding, channel formation and receptor assembly. At the postsynaptic membrane, the GlyR colocalizes with a 93-kDa tubulin-bind ing peripheral membrane protein, gephyrin. Antisense inhibition of gep hyrin expression prevents GlyR accumulation at postsynaptic membrane s pecialization. Thus, gephyrin is essential for postsynaptic receptor t opology.