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Gene Review

SLC17A6  -  solute carrier family 17 (vesicular...

Homo sapiens

Synonyms: DNPI, Differentiation-associated BNPI, Differentiation-associated Na(+)-dependent inorganic phosphate cotransporter, Solute carrier family 17 member 6, VGLUT2, ...
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Disease relevance of SLC17A6

  • By contrast, VGLUT2 was present in horizontal cells and ganglion cells in rat and human retina [1].
  • Here, we show that platelets express the pre-synaptic markers VGLUT1 and VGLUT2 and release glutamate following aggregation, implying a possible contributory role in the pathophysiology of stroke, migraine, and other excitotoxic disorders [2].
  • Confocal analysis of spinal cord sections at 8 weeks-12 months after ischemia revealed a continuing presence of ChAT positive alpha-motoneurons, Ia afferents and VGLUT2 and VGLUT1-positive terminals but a selective loss of small presumably inhibitory interneurons between laminae V-VII [3].

High impact information on SLC17A6

  • VGLUT3 also differs from VGLUT1 and VGLUT2 in its subcellular location, with somatodendritic as well as axonal expression [4].
  • Thus, VGLUT2 appears to possess two intrinsic transport machineries that are independent of each other: a DeltaPsi-dependent l-glutamate uptake and a Na(+)-dependent P(i) uptake [5].
  • The predicted amino acid sequence of hVGLUT3 shows 72% identity to both hVGLUT1 and hVGLUT2. hVGLUT3 functions as a vesicular glutamate transporter with similar properties to the other isoforms when it is heterologously expressed in a neuroendocrine cell line [6].
  • In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels [7].
  • Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels [7].

Biological context of SLC17A6


Anatomical context of SLC17A6


Associations of SLC17A6 with chemical compounds

  • Recently, two mammalian isoforms of a vesicular glutamate transporter, VGLUT1 and VGLUT2, have been identified, the expression of which enables quantal release of glutamate from glutamatergic neurons [6].
  • This increase in VGLUT2 mRNA was suppressed by actinomycin D [12].
  • VGLUT2 mRNA was significantly increased in beta- and alpha-cells by high and low glucose concentration, respectively [12].
  • These results indicate that VGLUT2 is expressed in subsets of A10 and A11 dopamine neurons, which might release dopamine and glutamate separately from different varicosities in the majority of their single axons [10].
  • Third, the recent cloning of 3 vesicular glutamate transporters (VGLUT1-3) has led to the discovery that noradrenergic neurons contain VGLUT2 mRNA, whereas 5-HT neurons contain VGLUT3 mRNA [13].

Regulatory relationships of SLC17A6


Other interactions of SLC17A6

  • Although mammalian VGLUT1 and VGLUT2 exhibit a complementary expression pattern covering all glutamatergic pathways in the CNS, expression of hVGLUT3 overlaps with them in some brain areas, suggesting molecular diversity that may account for physiological heterogeneity in glutamatergic synapses [6].
  • Reverse-transcriptase polymerase chain reaction analysis detected full-length VGLUT2 gene transcripts in the ventral midbrain [10].
  • A quantitative method is described for the measurement of N-mononitrosopiperazine (NPIP) and N,N'-dinitrosopiperazine (DNPIP) in drug formulations containing piperazine, using a gas chromatograph interfaced to a thermal energy analyzer (GC/TEA) [15].
  • The intraepithelial vagal sensory innervation of NEBs, on the other hand, appears to be myelinated and could be labelled by antibodies against VGLUT1, VGLUT2, CB and P2X3 receptors [16].

Analytical, diagnostic and therapeutic context of SLC17A6


  1. Distribution of vesicular glutamate transporters in rat and human retina. Gong, J., Jellali, A., Mutterer, J., Sahel, J.A., Rendon, A., Picaud, S. Brain Res. (2006) [Pubmed]
  2. Human platelets express the synaptic markers VGLUT1 and 2 and release glutamate following aggregation. Tremolizzo, L., DiFrancesco, J.C., Rodriguez-Menendez, V., Sirtori, E., Longoni, M., Cassetti, A., Bossi, M., El Mestikawy, S., Cavaletti, G., Ferrarese, C. Neurosci. Lett. (2006) [Pubmed]
  3. Development of GABA-sensitive spasticity and rigidity in rats after transient spinal cord ischemia: a qualitative and quantitative electrophysiological and histopathological study. Kakinohana, O., Hefferan, M.P., Nakamura, S., Kakinohana, M., Galik, J., Tomori, Z., Marsala, J., Yaksh, T.L., Marsala, M. Neuroscience (2006) [Pubmed]
  4. VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Fremeau, R.T., Voglmaier, S., Seal, R.P., Edwards, R.H. Trends Neurosci. (2004) [Pubmed]
  5. Vesicular glutamate transporter contains two independent transport machineries. Juge, N., Yoshida, Y., Yatsushiro, S., Omote, H., Moriyama, Y. J. Biol. Chem. (2006) [Pubmed]
  6. Molecular cloning and functional characterization of human vesicular glutamate transporter 3. Takamori, S., Malherbe, P., Broger, C., Jahn, R. EMBO Rep. (2002) [Pubmed]
  7. Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter. Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue, I., Kojima, I., Takeda, J. J. Neurochem. (2000) [Pubmed]
  8. Assignment of SLC17A6 (alias DNPI), the gene encoding brain/pancreatic islet-type Na+-dependent inorganic phosphate cotransporter to human chromosome 11p14.3. Aihara, Y., Onda, H., Teraoka, M., Yokoyama, Y., Seino, Y., Kasuya, H., Hori, T., Tomura, H., Inoue, I., Kojima, I., Takeda, J. Cytogenet. Cell Genet. (2001) [Pubmed]
  9. Differential development of vesicular glutamate transporters in brain: an in vitro study of cerebellar granule cells. Hallberg, O.E., Bogen, I.L., Reistad, T., Haug, K.H., Wright, M.S., Fonnum, F., Walaas, S.I. Neurochem. Int. (2006) [Pubmed]
  10. Particular subpopulations of midbrain and hypothalamic dopamine neurons express vesicular glutamate transporter 2 in the rat brain. Kawano, M., Kawasaki, A., Sakata-Haga, H., Fukui, Y., Kawano, H., Nogami, H., Hisano, S. J. Comp. Neurol. (2006) [Pubmed]
  11. Expression of vesicular glutamate transporter 1 immunoreactivity in peripheral and central endings of trigeminal mesencephalic nucleus neurons in the rat. Pang, Y.W., Li, J.L., Nakamura, K., Wu, S., Kaneko, T., Mizuno, N. J. Comp. Neurol. (2006) [Pubmed]
  12. Characterization of vesicular glutamate transporter in pancreatic alpha - and beta -cells and its regulation by glucose. Bai, L., Zhang, X., Ghishan, F.K. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  13. Glutamate co-transmission as an emerging concept in monoamine neuron function. Trudeau, L.E. Journal of psychiatry & neuroscience : JPN. (2004) [Pubmed]
  14. Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). Takamori, S., Rhee, J.S., Rosenmund, C., Jahn, R. J. Neurosci. (2001) [Pubmed]
  15. Analysis of piperazine drug formulations for N-nitrosamines. Dawson, B.A., Lawrence, R.C. Journal - Association of Official Analytical Chemists. (1987) [Pubmed]
  16. Sensory receptors in the airways: neurochemical coding of smooth muscle-associated airway receptors and pulmonary neuroepithelial body innervation. Brouns, I., De Proost, I., Pintelon, I., Timmermans, J.P., Adriaensen, D. Autonomic neuroscience : basic & clinical. (2006) [Pubmed]
  17. New method for contrast manipulation in DNP-enhanced MRI. Planinsic, G., Grucker, D., Stepisnik, J. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. (1996) [Pubmed]
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