Glycine transporters: essential regulators of synaptic transmission
- 20 January 2006
- journal article
- review article
- Published by Portland Press Ltd. in Biochemical Society Transactions
- Vol. 34 (1), 55-58
- https://doi.org/10.1042/bst0340055
Abstract
Glycine is a major inhibitory neurotransmitter in the mammalian CNS (central nervous system). Glycinergic neurotransmission is terminated by the uptake of glycine into glycinergic nerve terminals and neighbouring glial cells. This uptake process is mediated by specific Na+/Cl−-dependent GlyTs (glycine transporters), GlyT1 and GlyT2. GlyT1, in addition, is thought to regulate the concentration of glycine at excitatory synapses containing NMDARs (N-methyl-D-aspartate receptors), which require glycine as a co-agonist. We have analysed the physiological roles and regulation of GlyT1 and GlyT2 by generating transporter-deficient mice and searching for interacting proteins. Our genetic results indicate that at glycinergic synapses, the glial transporter GlyT1 catalyses the removal of glycine from the synaptic cleft, whereas GlyT2 is required for the re-uptake of glycine into nerve terminals, thereby allowing for neurotransmitter reloading of synaptic vesicles. Both GlyT1 and GlyT2 are essential for CNS function, as revealed by the lethal phenotypes of the respective knockout mice. Mice expressing only a single GlyT1 allele are phenotypically normal but may have enhanced NMDAR function. GlyT2 is highly enriched at glycinergic nerve terminals, and Ca2+-triggered exocytosis and internalization are thought to regulate GlyT2 numbers in the pre-synaptic plasma membrane. We have identified different interacting proteins that may play a role in GlyT2 trafficking and/or pre-synaptic localization.Keywords
This publication has 34 references indexed in Scilit:
- Cellular localization and subcellular distribution of Unc‐33‐like protein 6, a brain‐specific protein of the collapsin response mediator protein family that interacts with the neuronal glycine transporter 2Journal of Neurochemistry, 2005
- The neuronal glycine transporter 2 interacts with the PDZ domain protein syntenin-1Molecular and Cellular Neuroscience, 2004
- Localization of the GLYT1 Glycine Transporter at Glutamatergic Synapses in the Rat BrainCerebral Cortex, 2004
- The Second Intracellular Loop of the Glycine Transporter 2 Contains Crucial Residues for Glycine Transport and Phorbol Ester-induced RegulationOnline Journal of Public Health Informatics, 2004
- The therapeutic potential of glycine transporter-1 inhibitorsExpert Opinion on Investigational Drugs, 2004
- Calcium- and Syntaxin 1-mediated Trafficking of the Neuronal Glycine Transporter GLYT2Online Journal of Public Health Informatics, 2001
- Developmental Expression of the Glycine Transporters GLYT1 and GLYT2 in Mouse BrainJournal of Neurochemistry, 1996
- Modulation of a Recombinant Glycine Transporter (GLYT1b) by Activation of Protein Kinase CJournal of Neurochemistry, 1995
- Regional Distribution and Developmental Variation of the Glycine Transporters GLYT1 and GLYT2 in the Rat CNSEuropean Journal of Neuroscience, 1995
- Regulation by phorbol esters of the glycine transporter (GLYT1) in glioblastoma cellsBiochimica et Biophysica Acta (BBA) - Biomembranes, 1995