Review : Glycine Receptors: Molecular Heterogeneity and Implications for Disease

Abstract

The inhibitory glycine receptor is a ligand-gated chloride channel that exists in developmentally regulated isoforms. These oligomeric transmembrane proteins are composed of variants of the ligand binding α subunit and structural β polypeptides. The agonist and antagonist sites of the α subunits are formed by discontinuous sequence motifs. In the murine genome, the genes encoding the α1 ( Glra1), α3 ( Glra3), and β ( Glyrb) subunit are autosomally located, whereas the α2 ( Glra2) and α4 ( Glra4) genes reside on the X-chromosome. Mutations of glycine receptor genes have been found to underly hypertonic motor disorders in mice and humans. The mouse mutants spasmodic (spd) and oscillator ( spdot) carry recessive mutations of the Glra 1 gene. In the phenotypically similar mouse mutant spastic ( spa), the intronic insertion of a LINE-1 transposable element into the Gyrb gene results in the aberrant splicing and a consecutive loss of glycine receptors. The human neurological disorder hyperekplexia (startle disease, stiff baby syndrome) is caused by point mutations within the α1 subunit gene ( GLRA1) localized in the human chromosomal region 5q31.3. The Neuroscientist 1:130- 141,1995