Disease relevance of SLC17A7

• 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 [1].
• 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 [2].

Psychiatry related information on SLC17A7

• Using fluorescent in situ hybridization, we localized hBNPI to the long arm of chromosome 19 (19q13) in close proximity to the late-onset familial Alzheimer's disease locus [3].

High impact information on SLC17A7

• Stimulation of exocytosis--fusion of the vesicles with the cell membrane and release of their contents--resulted in quantal release of glutamate from BNPI-expressing cells [4].
• Furthermore, we expressed BNPI in neurons containing GABA (gamma-aminobutyric acid) and maintained them as cultures of single, isolated neurons that form synapses to themselves [4].
• We conclude that BNPI functions as vesicular glutamate transporter and that expression of BNPI suffices to define a glutamatergic phenotype in neurons [4].
• VGLUT3 also differs from VGLUT1 and VGLUT2 in its subcellular location, with somatodendritic as well as axonal expression [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].

Biological context of SLC17A7

• The level of hBNPI mRNA is quite low in fetal compared with adult human brain, suggesting developmental regulation of hBNPI gene expression [3].
• The distribution of VGLUT1 and VGLUT2 accounts for the ability of most established excitatory neurons to release glutamate by exocytosis [5].
• The transport characteristics are similar to the cloned neuronal VGLUT1 and -2 in regard to ATP dependence, substrate specificity, kinetics, and chloride dependence [7].
• The results indicate both that cerebellar granule cells are mature at approximately 7 days in vitro, and that the up-regulation of VGLUT1 and down-regulation of VGLUT2 in cerebellar granule cells are both independent of surrounding astrocytes and neuronal input [8].

Anatomical context of SLC17A7

• Northern blot analysis demonstrates that hBNPI mRNA is expressed predominantly in brain and most abundantly in neuron-enriched regions such as the amygdala and hippocampus [3].
• Expression of hBNPI in COS-1 cells results in Na(+)-dependent P(i) uptake [3].
• In situ hybridization histochemistry reveals relatively high levels of hBNPI mRNA in pyramidal neurons of the cerebral cortex and hippocampus and in granule neurons of dentate gyrus [3].
• 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 [9].
• It has recently been suggested that the brain-specific Na+-dependent phosphate inorganic co-transporter (BNPI) is able to support glutamate transport and storage in synaptic vesicles [10].

Associations of SLC17A7 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].
• Identification of Endophilins 1 and 3 as Selective Binding Partners for VGLUT1 and Their Co-Localization in Neocortical Glutamatergic Synapses: Implications for Vesicular Glutamate Transporter Trafficking and Excitatory Vesicle Formation [11].
• Within the myenteric neuropil we found, besides co-localization of VGLUT1 and substance P, no further co-localization of VGLUT1-ir with any of these markers [12].

Co-localisations of SLC17A7

• 3. We also show that endophilin 1 and endophilin 3 co-localize with VGLUT1 in synaptic terminals of differentiated rat neocortical neurons in primary culture [11].

Regulatory relationships of SLC17A7

• Northern blot and in situ hybridization analyses indicate that DNPI mRNA is expressed in some brain regions in which VGLUT1 mRNA is not expressed [13].

Other interactions of SLC17A7

• 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].
• In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC [14].
• Bidirectional and opposite activity-dependent regulation of VGLUT1 and VIAAT expression would serve to adjust the balance of glutamate and GABA release and therefore the level of postsynaptic receptor saturation [15].
• We screened a yeast two-hybrid library with bait containing the C-terminal amino acids of VGLUT1 and obtained clones that encode endophilin 1 and endophilin 3, proteins considered to play an integral role in glutamatergic vesicle formation [11].
• We show that chronic excitatory synapse deprivation generates an excitable CA3 network where enhanced amplitude and frequency of spontaneous excitatory post-synaptic potentials were associated with increased glutamate receptor subunit expression and increased number and size of synapsin 1 and VGLUT1 positive puncta [16].

Analytical, diagnostic and therapeutic context of SLC17A7

• We describe the molecular cloning of a cDNA encoding a human brain Na(+)-dependent inorganic phosphate (P(i)) cotransporter (hBNPI) [3].
• Their contents in BNPI mRNA were compared by RT-PCR [10].
• Electron microscopy after dual immunolabeling for VGLUT1/CTb by the VGLUT1/immunoperoxidase and CTb/immunogold-silver methods further revealed synaptic contact of VGLUT1- and CTb-immunopositive axon terminals upon CTb-labeled neuronal profiles within the Vm [17].

References