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Gene Review

Slc6a5  -  solute carrier family 6 (neurotransmitter...

Rattus norvegicus

Synonyms: GlyT-2, GlyT2, Glyt2, Sodium-and chloride-dependent glycine transporter 2, Solute carrier family 6 member 5
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High impact information on Slc6a5


Biological context of Slc6a5


Anatomical context of Slc6a5

  • Incubation of a GlyT2 N-terminal fusion protein with spinal cord extract in the presence of calcium followed by protein sequence analysis localized the major N-terminal cleavage site after methionine 156, with a second cleavage site being situated after glycine 164 [5].
  • Our data suggest that Ca2+-triggered proteolysis may contribute to the regulation of GlyT2 trafficking and/or function in the neuronal plasma membrane [5].
  • We report that activation of a Ca2+-dependent protease, most likely calpain, in spinal cord synaptosomes or cultured spinal cord neurons, results in partial proteolysis of GlyT2 [5].
  • Subcellular fractionation of spinal cord and retina homogenates at different developmental stages showed Ulip6 immunoreactivity to be associated with light vesicles that were distinct from GlyT2-containing and synaptic vesicles [3].
  • Decreases in auditory primary afferent activity, caused by either unilateral labyrinthectomy or disruption of the middle ear ossicles, caused a reduction in Glyt2, but not Glyt1 mRNA in the ipsilateral DCN and in the contralateral medial nucleus of the trapezoid body [4].

Associations of Slc6a5 with chemical compounds

  • Typical antipsychotics haloperidol, thioridazine and chlorpromazine non-selectively inhibited [(14)C]glycine uptake mediated by GlyT1a and GlyT2 with potency of 9-21 microM [6].
  • In the ventral horn a presynaptic location was confirmed by co-localization of Kv3.4-IR with the synaptic vesicle protein, SV2 and also with the glutamate vesicle markers vesicular glutamate transporter (VGluT) 1, VGluT2 or the glycine transporter GlyT2, suggesting a role for the channel in both excitatory and inhibitory neurotransmission [7].

Other interactions of Slc6a5

  • Org 25935 is an inhibitor of the glycine transporter 1 (GlyT1) protein with negligible action on the glycine transporter 2 (GlyT2) protein [8].
  • PRV immunohistochemistry combined with ISH for both GlyT2 and GAD-67 mRNAs showed that at least 63% of midline medulla GABAergic PS neurons were also glycinergic and 76% of glycinergic PS neurons were GABAergic [9].

Analytical, diagnostic and therapeutic context of Slc6a5

  • Immunocytochemistry revealed punctate Ulip6 immunoreactivity in both somatic regions and processes of cultured spinal neurones; no colocalization with GlyT2 or other synaptic marker proteins was found [3].
  • Acoustic stimulation at either 10 kHz or 40 kHz was used to provide controlled increases in primary afferent activity, evoking localized increases in Glyt2 mRNA in clusters of neurons in the DCN [4].


  1. The neuronal glycine transporter 2 interacts with the PDZ domain protein syntenin-1. Ohno, K., Koroll, M., El Far, O., Scholze, P., Gomeza, J., Betz, H. Mol. Cell. Neurosci. (2004) [Pubmed]
  2. Morphologically identified glycinergic synapses in the hippocampus. Danglot, L., Rostaing, P., Triller, A., Bessis, A. Mol. Cell. Neurosci. (2004) [Pubmed]
  3. 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 2. Horiuchi, M., Loebrich, S., Brandstaetter, J.H., Kneussel, M., Betz, H. J. Neurochem. (2005) [Pubmed]
  4. Neuronally modulated transcription of a glycine transporter in rat dorsal cochlear nucleus and nucleus of the medial trapezoid body. Barmack, N.H., Guo, H., Kim, H.J., Qian, H., Qian, Z. J. Comp. Neurol. (1999) [Pubmed]
  5. Calpain-mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2. Baliova, M., Betz, H., Jursky, F. J. Neurochem. (2004) [Pubmed]
  6. Effects of typical and atypical antipsychotics on human glycine transporters. Williams, J.B., Mallorga, P.J., Jeffrey Conn, P., Pettibone, D.J., Sur, C. Schizophr. Res. (2004) [Pubmed]
  7. Association of potassium channel Kv3.4 subunits with pre- and post-synaptic structures in brainstem and spinal cord. Brooke, R.E., Atkinson, L., Batten, T.F., Deuchars, S.A., Deuchars, J. Neuroscience (2004) [Pubmed]
  8. The glycine reuptake inhibitor org 25935 decreases ethanol intake and preference in male wistar rats. Molander, A., Lid??, H.H., L??f, E., Ericson, M., S??derpalm, B. Alcohol Alcohol. (2007) [Pubmed]
  9. GABAergic and glycinergic presympathetic neurons of rat medulla oblongata identified by retrograde transport of pseudorabies virus and in situ hybridization. Stornetta, R.L., McQuiston, T.J., Guyenet, P.G. J. Comp. Neurol. (2004) [Pubmed]
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