Disease relevance of Slc17a6

• In retina, glutamatergic photoreceptors and bipolar cells exclusively express the VGLUT1 isoform, whereas ganglion cells express VGLUT2 [1].

High impact information on Slc17a6

• We report here the molecular cloning and functional characterization of a novel glutamate transporter, VGLUT2, from mouse brain [2].
• VGLUT2 has all major functional characteristics of a synaptic vesicle glutamate transporter, including ATP dependence, chloride stimulation, substrate specificity, and substrate affinity [2].
• In addition, VGLUT2 activity is dependent on both membrane potential and pH gradient of the electrochemical proton gradient, whereas VGLUT1 is primarily dependent on only membrane potential [2].
• Synaptic and vesicular co-localization of the glutamate transporters VGLUT1 and VGLUT2 in the mouse hippocampus [3].
• Indeed, indirect evidence obtained in young VGLUT1-deficient mice indicated that in cells that co-express VGLUT1 and VGLUT2, the transporters may be targeted to different synaptic vesicles, which may populate different types of synapses formed by the same neurone [3].

Anatomical context of Slc17a6

• We show here that VGLUT1 and VGLUT2 are co-localized in many layers of the young hippocampus [3].
• There is agreement that the VGLUTs are differentially expressed in brain, and that two isoforms, VGLUT1 and VGLUT2, are localized to excitatory axon terminals in the cerebellar cortex [4].
• Three transporters (VGLUT1-VGLUT3) are expressed in the mammalian CNS, with partial overlapping expression patterns, and VGLUT2 is the most abundantly expressed paralog in the thalamus, midbrain, and brainstem [5].
• Double-labeling immunoelectronmicroscopy confirmed the association of VGLUT2 with GLP-1-containing secretory granules [6].
• We have shown that intestinal L cells express VGLUT2, a VGLUT isoform, which suggests that L cells secrete L-glutamate [6].

Associations of Slc17a6 with chemical compounds

• Within the RVLM, 79% of the bulbospinal C1 cells contained DNPI/VGLUT2 mRNA [7].
• DNPI/VGLUT2 mRNA was detected in most of the adrenergic neurons of the C1, C2, and C3 groups (75-80% of TH-ir neurons), in the A2 noradrenergic group (80%), and in vast numbers of area postrema cells [8].
• In seven barbiturate-anesthetized rats, 16 vasomotor presympathetic neurons were filled with biotinamide and analyzed for the presence of tyrosine hydroxylase immunoreactivity and/or DNPI/VGLUT2 mRNA [7].

Co-localisations of Slc17a6

• Double-labelling studies showed that VGLUT1 and VGLUT2 colocalized fully with synapsin I and/or II in the hippocampus and neostriatum, respectively [9].

Other interactions of Slc17a6

• We consider it possible that expressions of CR with VGLUT1/VGLUT2 and mGluR1alpha(+) with VGLUT1 in the two subsets of vestibulocerebellar UBCs are determined by specific vestibular inputs, carried by groups of primary and/or secondary vestibular afferents [4].
• Here, we show that CB1 receptors are primarily located on GABAergic (vesicular GABA transporter-positive) and glutamatergic [vesicular glutamate transporter-1 (VGLUT-1)- and VGLUT-2-positive] striatal nerve terminals and are present in the presynaptic active zone, in the postsynaptic density, as well as in the extrasynaptic membrane [10].

Analytical, diagnostic and therapeutic context of Slc17a6

• Double immunofluorescence and confocal microscopy showed that mossy terminals of CR-positive (CR(+)) UBCs were immunoreactive for VGLUT1 and VGLUT2, while mossy terminals of mGluR1alpha-positive (mGluR1alpha(+)) UBCs were provided with VGLUT1 only [4].
• Western blot analysis revealed immunological counterparts for VGLUT2, whereas an immunological counterpart of VGLUT1 was not detected [6].
• Indirect immunofluorescence microscopy revealed a punctate distribution of VGLUT2 immunoreactivity throughout the cells, which co-localized with GLP-1 [6].
• RT-PCR and northern blot analyses revealed expression of the VGLUT1 and VGLUT2 genes, but not of the VGLUT3 gene [6].
• By using a double in situ hybridization method, the presence of the mRNA for DNPI/VGLUT2 and glutamic acid decarboxylase (GAD)-67 was mutually exclusive [8].

References