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SLC6A9  -  solute carrier family 6 (neurotransmitter...

Homo sapiens

Synonyms: GLYT1, GlyT-1, GlyT1, Sodium-and chloride-dependent glycine transporter 1, Solute carrier family 6 member 9
 
 
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Disease relevance of SLC6A9

  • Human placental choriocarcinoma (JAR) cells endogenously expressing glycine transporter type 1a (GlyT1a) have been cultured in 96-well scintillating microplates to develop a homogenous screening assay for the detection of GlyT1 antagonists [1].
 

High impact information on SLC6A9

 

Biological context of SLC6A9

 

Anatomical context of SLC6A9

 

Associations of SLC6A9 with chemical compounds

  • A chimeric GLYT2 (GLYT2a-EL1) that contains GLYT1 sequences in this region, including the relevant cysteine, was sensitive to the reagent, and its sensitivity was decreased by co-substrates [10].
  • GLYT1 is selectively inhibited by the sarcosine derivative N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-propyl]sarcosine (NFPS) [11].
  • GLYT1, expressed in glial processes of glycinergic areas and in glia and neurons of glutamatergic pathways that contain N-methyl-d-aspartate (NMDA) receptors, is essential for regulating glycine levels both at glycinergic and NMDA-containing synapses [11].
  • Differential effects of ethanol on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters [12].
  • The synaptic action of glycine is terminated by two sodium- and chloride-coupled transporters, GLYT1 and GLYT2, located in the glial plasma membrane and in the presynaptic terminals, respectively [13].
 

Other interactions of SLC6A9

  • Two forms of glycine transporter have been described to date, GlyT-1 and GlyT-2 [14].
  • It is expected that non-transportable, non-competitive inhibitors of GlyT1 may have therapeutic value in CNS disorders characterized by hypofunctional NMDA receptor-mediated glutamatergic neurotransmission [15].
  • Blockade of selective GLT-1 (EAAT2) and GlyT1, as well as nonspecific transporters, did not inhibit or had no effect on uptake of aluminum in complex with the corresponding amino acids [16].

References

  1. Development of a scintillation proximity assay for analysis of Na+/Cl- -dependent neurotransmitter transporter activity. Williams, J.B., Mallorga, P.J., Lemaire, W., Williams, D.L., Na, S., Patel, S., Conn, J.P., Pettibone, D.J., Austin, C., Sur, C. Anal. Biochem. (2003) [Pubmed]
  2. Glycine supply to human enterocytes mediated by high-affinity basolateral GLYT1. Christie, G.R., Ford, D., Howard, A., Clark, M.A., Hirst, B.H. Gastroenterology (2001) [Pubmed]
  3. Zn2+ inhibits glycine transport by glycine transporter subtype 1b. Ju, P., Aubrey, K.R., Vandenberg, R.J. J. Biol. Chem. (2004) [Pubmed]
  4. Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization. Jones, E.M., Fernald, A., Bell, G.I., Le Beau, M.M. Cytogenet. Cell Genet. (1995) [Pubmed]
  5. The role of N-glycosylation in the targeting and activity of the GLYT1 glycine transporter. Olivares, L., Aragón, C., Giménez, C., Zafra, F. J. Biol. Chem. (1995) [Pubmed]
  6. 4-Substituted-8-(1-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with superior pharmacological and pharmacokinetic parameters. Alberati, D., Hainzl, D., Jolidon, S., Kurt, A., Pinard, E., Thomas, A.W., Zimmerli, D. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  7. Glyt-1 expression in cultured human Müller cells and intact retinae. Reye, P., Penfold, P., Pow, D.V. Glia (2001) [Pubmed]
  8. ALX 5407: a potent, selective inhibitor of the hGlyT1 glycine transporter. Atkinson, B.N., Bell, S.C., De Vivo, M., Kowalski, L.R., Lechner, S.M., Ognyanov, V.I., Tham, C.S., Tsai, C., Jia, J., Ashton, D., Klitenick, M.A. Mol. Pharmacol. (2001) [Pubmed]
  9. Glycine transporter isoforms show differential subcellular localization in PC12 cells. Geerlings, A., Núñez, E., Rodenstein, L., López-Corcuera, B., Aragón, C. J. Neurochem. (2002) [Pubmed]
  10. Substrate-induced conformational changes of extracellular loop 1 in the glycine transporter GLYT2. López-Corcuera, B., Núñez, E., Martínez-Maza, R., Geerlings, A., Aragón, C. J. Biol. Chem. (2001) [Pubmed]
  11. Transmembrane domains 1 and 3 of the glycine transporter GLYT1 contain structural determinants of N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-propyl]sarcosine specificity. Núñez, E., Martínez-Maza, R., Geerlings, A., Aragón, C., López-Corcuera, B. Neuropharmacology (2005) [Pubmed]
  12. Differential effects of ethanol on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters. Núñez, E., López-Corcuera, B., Martínez-Maza, R., Aragón, C. Br. J. Pharmacol. (2000) [Pubmed]
  13. Molecular biology of glycinergic neurotransmission. Zafra, F., Aragón, C., Giménez, C. Mol. Neurobiol. (1997) [Pubmed]
  14. Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter. Evans, J., Herdon, H., Cairns, W., O'Brien, E., Chapman, C., Terrett, J., Gloger, I. FEBS Lett. (1999) [Pubmed]
  15. Glycine transporter type-1 and its inhibitors. Harsing, L.G., Juranyi, Z., Gacsalyi, I., Tapolcsanyi, P., Czompa, A., Matyus, P. Current medicinal chemistry. (2006) [Pubmed]
  16. Accumulation of aluminum by primary cultured astrocytes from aluminum amino acid complex and its apoptotic effect. Aremu, D.A., Meshitsuka, S. Brain Res. (2005) [Pubmed]
 
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