Glycinergic transmission.
Inhibition in the mature central nervous system is mediated by activation of gamma-aminobutyric acid (GABA(A)) and glycine receptors. Both receptors belong to the same superfamily of ligand-gated ion channels and share common transmembrane topology and structural and functional features. Glycine receptors are pentameric ligand-gated anion channels composed of two different subunits, named alpha und beta, that assemble with a fixed stoichiometric ratio of two alpha to three beta subunits. Four genes encoding the alpha subunits exist, whereas only one gene encoding the beta subunit has been detected. Ligand binding occurs at the interface of alpha and beta subunits. The beta subunit, which is unable to form homo-oligomeric receptors, is responsible for assembly and channel properties. Moreover, this subunit carries a binding motif for the cytoplasmic protein gephyrin, which is believed to mediate synaptic clustering and anchoring at inhibitory synapses by interacting with the subsynaptic cytoskeleton. Synaptic gephyrin appears to restrict the mobility of glycine receptors diffusing in the plane of the plasma membrane, thereby generating dynamic plasma membrane domains contributing to the plasticity of inhibitory synapses. Glycine receptors are well established as playing important roles in controlling motor functions and sensory signaling in vision and audition and those in the dorsal horn of the spinal cord are now considered to be new targets for pain therapies. Like GABA(A) receptors, glycine receptors have been shown to be depolarizing during development. The functional meaning of the developmental switch from excitatory to inhibitory glycine receptor action remains to be elucidated.
Kirsch
Joachim
J
Institute for Anatomy and Cell Biology, Department of Medical Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany. joachim.kirsch@urz.uni-heidelberg.de
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D006309:Hearing / Q000235:genetics; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009433:Neural Inhibition / Q000235:genetics; D010146:Pain / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D014785:Vision, Ocular / Q000235:genetics
D002352:Carrier Proteins; D007473:Ion Channels; D008024:Ligands; D008565:Membrane Proteins; D021122:Protein Subunits; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; C073441:gephyrin