GlyT2

• グリシン輸送体2

関

glycine transporter 2

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/22 23:53:10」(JST)

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Solute carrier family 6 (neurotransmitter transporter), member 5
Identifiers
Symbols	SLC6A5 ; GLYT-2; GLYT2; HKPX3; NET1
External IDs	OMIM: 604159 MGI: 105090 HomoloGene: 37901 ChEMBL: 3060 GeneCards: SLC6A5 Gene
Gene ontology Molecular function • neurotransmitter:sodium symporter activity • glycine:sodium symporter activity Cellular component • plasma membrane • integral component of plasma membrane • integral component of membrane Biological process • transport • neurotransmitter transport • synaptic transmission • glycine import • transmembrane transport • synaptic transmission, glycinergic Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9152	104245
Ensembl	ENSG00000165970	ENSMUSG00000039728
UniProt	Q9Y345	Q761V0
RefSeq (mRNA)	NM_004211	NM_001146013
RefSeq (protein)	NP_004202	NP_001139485
Location (UCSC)	Chr 11: 20.6 – 20.66 Mb	Chr 7: 49.91 – 49.96 Mb
PubMed search	[1]	[2]

Glycine transporter 2 (GlyT2) also known as the sodium- and chloride-dependent glycine transporter 2 or solute carrier family 6 member 5 is a protein that in humans is encoded by the SLC6A5 gene.

The glycine transporter 2 is a membrane protein which recaptures glycine, a major inhibitory transmitter in the spinal cord and brainstem. GlyT2 is a specific marker of glycinergic neurons and a member of the Na⁺ and Cl⁻-coupled transporter family SLC6. Glycine uptake mediated by GlyT2 is electrogenic, coupled to three Na⁺ and one Cl⁻ (i.e. two positive charges per glycine). In humans, GlyT2 is encoded by the SLC6A5 gene. Inactivation of GlyT2 in knockout mice is lethal during the second post-natal week as the absence of GlyT2 disrupts inhibitory transmission by reducing glycine release. Mutations in SLC6A5 gene are responsible for a presynaptic form of hyperekplexia, a genetic disease causing increased startle reflex. GlyT2 main physiological role is to recapture glycine released in the synaptic cleft and to maintain high glycine concentration in the presynaptic neuron. Therefore chronic inhibition of GlyT2 will deplete intracellular storage of glycine and limit its accumulation in synaptic vesicles.

See also

• Sodium:neurotransmitter symporter
• Solute carrier family

References

Further reading

• López-Corcuera B, Aragón C, Geerlings A (2002). "Regulation of glycine transporters.". Biochem. Soc. Trans. 29 (Pt 6): 742–5. doi:10.1042/BST0290742. PMID 11709067. 
• Gallagher MJ, Burgess LH, Brunden KR (1999). "Characterization of multiple forms of the human glycine transporter type-2.". Brain Res. Mol. Brain Res. 70 (1): 101–15. doi:10.1016/S0169-328X(99)00135-7. PMID 10381548. 
• Evans J, Herdon H, Cairns W et al. (2000). "Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter.". FEBS Lett. 463 (3): 301–6. doi:10.1016/S0014-5793(99)01636-1. PMID 10606742.  CS1 maint: Explicit use of et al. (link)
• Martínez-Maza R, Poyatos I, López-Corcuera B et al. (2001). "The role of N-glycosylation in transport to the plasma membrane and sorting of the neuronal glycine transporter GLYT2.". J. Biol. Chem. 276 (3): 2168–73. doi:10.1074/jbc.M006774200. PMID 11036075.  CS1 maint: Explicit use of et al. (link)
• Geerlings A, Núñez E, Rodenstein L et al. (2002). "Glycine transporter isoforms show differential subcellular localization in PC12 cells.". J. Neurochem. 82 (1): 58–65. doi:10.1046/j.1471-4159.2002.00930.x. PMID 12091465.  CS1 maint: Explicit use of et al. (link)
• Baliova M, Betz H, Jursky F (2004). "Calpain-mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2.". J. Neurochem. 88 (1): 227–32. doi:10.1046/j.1471-4159.2003.02192.x. PMID 14675166. 
• Jamra RA, Villela AW, Klein K et al. (2006). "No association between genetic variants at the GLYT2 gene and bipolar affective disorder and schizophrenia.". Psychiatr. Genet. 16 (3): 91. doi:10.1097/01.ypg.0000199450.07786.ab. PMID 16691125.  CS1 maint: Explicit use of et al. (link)
• Rees MI, Harvey K, Pearce BR et al. (2006). "Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease.". Nat. Genet. 38 (7): 801–6. doi:10.1038/ng1814. PMC 3204411. PMID 16751771.  CS1 maint: Explicit use of et al. (link)
• Roux M, Supplisson. (2000). "Neuronal and glial glycine transporters have different stoichiometries.". Neuron 25 (2): 373–83. doi:10.1016/s0896-6273(00)80901-0. PMID 10719892. 
• Aubrey K, Rossi FM, “ et al. (2007). "The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype.". J. Neurosci 27 (23): 6273–81. doi:10.1523/JNEUROSCI.1024-07.2007. PMID 17554001.  CS1 maint: Explicit use of et al. (link)
• Rousseau F, Aubrey KR, Supplisson S. (2008). "The glycine transporter GlyT2 controls the dynamics of synaptic vesicle refilling in inhibitory spinal cord neurons..". J. Neurosci 28 (39): 9755–68. doi:10.1523/JNEUROSCI.0509-08.2008. PMID 18815261. 
• Eulenburg V, Becker K, Gomeza J et al. (2006). "Mutations within the human GLYT2 (SLC6A5) gene associated with hyperekplexia.". Biochem. Biophys. Res. Commun. 348 (2): 400–5. doi:10.1016/j.bbrc.2006.07.080. PMID 16884688.  CS1 maint: Explicit use of et al. (link)

UpToDate Contents

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• 1. 小児における運動過多な運動障害 hyperkinetic movement disorders in children

English Journal

• A new function for glycine GlyT2 transporters: Stimulation of γ-aminobutyric acid release from cerebellar nerve terminals through GAT1 transporter reversal and Ca(2+) -dependent anion channels.

• Milanese M, Romei C, Usai C, Oliveri M, Raiteri L.Author information Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, Italy; Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.AbstractGlycine GlyT2 transporters are localized on glycine-storing nerve endings. Their main function is to accumulate glycine to replenish synaptic vesicles. Glycine was reported to be costored with γ-aminobutyric acid (GABA) in cerebellar interneurons that may coexpress glycine and GABA transporters, and this is confirmed here by confocal microscopy analysis showing coexpression of GAT1 and GlyT2 transporters on microtubule-associated protein-2-positive synaptosomes. It was found that GABA uptake elicited glycine release from cerebellar nerve endings by various mechanisms. We investigated whether and by what mechanisms activation of glycine transporters could mediate release of GABA. Nerve endings purified from cerebellum were prelabeled with [(3) H]GABA and exposed to glycine. Glycine stimulated [(3) H]GABA release in a concentration-dependent manner. The glycine effect was insensitive to strychnine or to 5,7-dichlorokynurenate but it was abolished when GlyT2 transporters were blocked. About 20% of the evoked release was dependent on external Ca(2+) entered by reversal of plasmalemmal Na(+) /Ca(2+) exchangers. A significant portion of the GlyT2-mediated release of [(3) H]GABA (about 50% of the external Ca(2+) -independent release) occurred by reversal of GABA GAT1 transporters. Na(+) ions, reaching the cytosol during glycine uptake through GlyT2, activated mitochondrial Na(+) /Ca(2+) exchangers, causing an increase in cytosolic Ca(2+) , which in turn triggered a Ca(2+) -induced Ca(2+) release process at inositoltrisphosphate receptors. Finally, the increased availability of Ca(2+) in the cytosol allowed the opening of anion channels permeable to GABA. In conclusion, GlyT2 transporters not only take up glycine to replenish synaptic vesicles but can also mediate release of GABA by reversal of GAT1 and permeation through anion channels. © 2013 Wiley Periodicals, Inc.
• Journal of neuroscience research.J Neurosci Res.2014 Mar;92(3):398-408. doi: 10.1002/jnr.23321. Epub 2013 Nov 23.
• Glycine GlyT2 transporters are localized on glycine-storing nerve endings. Their main function is to accumulate glycine to replenish synaptic vesicles. Glycine was reported to be costored with γ-aminobutyric acid (GABA) in cerebellar interneurons that may coexpress glycine and GABA transporters, an
• PMID 24273061

• Morphological, Biophysical and Synaptic Properties of Glutamatergic Neurons of the Mouse Spinal Dorsal Horn.

• Punnakkal P, von Schoultz C, Haenraets K, Wildner H, Zeilhofer HU.Author information University of Zurich, Switzerland.AbstractInterneurons of the spinal dorsal horn take a centre stage in somatosensory and nociceptive processing. A mechanistic understanding of their function depends on profound knowledge of their intrinsic properties and their integration into dorsal horn circuits. Here, we have used BAC transgenic mice expressing eGFP under the control of the vGluT2 gene (vGluT2-eGFP mice) to perform a detailed electrophysiological and morphological characterization of excitatory dorsal horn neurons, and to compare their properties to those of GABAergic (Gad67-eGFP tagged) and glycinergic (GlyT2-eGFP tagged) neurons. vGluT2-eGFP was detected in about one third of all excitatory dorsal horn neurons that, as demonstrated by the coexpression of vGluT2-eGFP with different markers of subtypes of glutamatergic neurons, likely labelled a representative fraction of these neurons. Three types of dendritic tree morphologies (vertical, central, and radial), but no islet cell-type morphology, were identified in vGluT2-eGFP neurons. vGluT2-eGFP neurons had more depolarised action potential thresholds and longer action potential durations than inhibitory neurons, while no significant differences were found for the resting membrane potential, input resistance, cell capacitance and after-hyperpolarisation. Delayed firing and single action potential firing were the single most prevalent firing patterns in vGluT2-eGFP neurons of the superficial and deep dorsal horn, respectively. By contrast, tonic firing prevailed in inhibitory interneurons of the dorsal horn. Capsaicin-induced synaptic inputs were detected in about half of the excitatory and inhibitory neurons, and occurred more frequently in superficial than in deep dorsal horn neurons. Primary afferent-evoked (polysynaptic) inhibitory inputs were found in the majority of glutamatergic and glycinergic neurons, but only in less than half of the GABAergic population. Excitatory dorsal horn neurons thus differ from their inhibitory counterparts in several biophysical properties and possibly also in their integration into the local neuronal circuitry.
• The Journal of physiology.J Physiol.2014 Jan 6. [Epub ahead of print]
• Interneurons of the spinal dorsal horn take a centre stage in somatosensory and nociceptive processing. A mechanistic understanding of their function depends on profound knowledge of their intrinsic properties and their integration into dorsal horn circuits. Here, we have used BAC transgenic mice ex
• PMID 24324003

• Identification of initially appearing glycine-immunoreactive neurons in the embryonic zebrafish brain.

• Moly PK, Ikenaga T, Kamihagi C, Tariqul Islam AF, Hatta K.Author information Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori, Ako-gun, Hyogo, 678-1297, Japan.AbstractGlycine is a major inhibitory neurotransmitter in the central nervous system of vertebrates. Here, we report the initial development of glycine-immunoreactive (Gly-ir) neurons and fibers in zebrafish. The earliest Gly-ir cells were found in the hindbrain and rostral spinal cord by 20 h post-fertilization (hpf). Gly-ir cells in rhombomeres 5 and 6 that also expressed glycine transporter 2 (glyt2) mRNA were highly stereotyped; they were bilaterally located and their axons ran across the midline and gradually turned caudally, joining the medial longitudinal fascicles in the spinal cord by 24 hpf. Gly-ir neurons in rhombomere 5 were uniquely identified, since there was one per hemisegment, whereas the number of Gly-ir neurons in rhombomere 6 were variable from one to three per hemisegment. Labeling of these neurons by single-cell electroporation and tracing them until the larval stage revealed that they became MiD2cm and MiD3cm, respectively. The retrograde labeling of reticulo-spinal neurons in Tg(glyt2:gfp) larva, which express GFP in Gly-ir cells, and a genetic mosaic analysis with glyt2:gfp DNA construct also supported this notion. Gly-ir cells were also distributed widely in the anterior brain by 27 hpf, whereas glyt2 was hardly expressed. Double staining with anti-glycine and anti-GABA antibodies demonstrated distinct distributions of Gly-ir and GABA-ir cells, as well as the presence of doubly immunoreactive cells in the brain and placodes. These results provide evidence of identifiable glycinergic (Gly-ir/glyt2-positive) neurons in vertebrate embryos, and they can be used in further studies of the neurons' development and function at the single-cell level. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2014.
• Developmental neurobiology.Dev Neurobiol.2013 Dec 9. doi: 10.1002/dneu.22158. [Epub ahead of print]
• Glycine is a major inhibitory neurotransmitter in the central nervous system of vertebrates. Here, we report the initial development of glycine-immunoreactive (Gly-ir) neurons and fibers in zebrafish. The earliest Gly-ir cells were found in the hindbrain and rostral spinal cord by 20 h post-fertiliz
• PMID 24318965

Japanese Journal

• Orexin neurons receive glycinergic innervations

• PLoS ONE 6(9), e25076, 2011-09-16
• NAID 120003497597

• Orexin neurons receive glycinergic innervations.

• PloS one 6(9), e25076, 2011
• NAID 120003959469

• Orexin neurons receive glycinergic innervations

• PloS one 6(9), e25076-1-e25076-12, 2011
• NAID 120003851399

Related Pictures

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★リンクテーブル★

リンク元	「グリシン輸送体2」「glycine transporter 2」

「グリシン輸送体2」

　　[★]

英

glycine transporter 2、GlyT2

関

細胞膜グリシントランスポーター、グリシントランスポーター、グリシン輸送体1、グリシントランスポーター2

「glycine transporter 2」

　　[★]

• グリシン輸送体2、グリシントランスポーター2

関

glycine plasma membrane transport protein、glycine transporter、glycine transporter 1、GlyT2