Disease relevance of Slc17a7

• Punctate BNPI immunoreactivity was localized in the inner and outer plexiform layers, and weak DNPI immunoreactivity was detectable only in some cells and fibers of the ganglion cell layer [1].

High impact information on Slc17a7

• Fluorescently tagged VGLUT-containing vesicles were studied dynamically in living astrocytes by total internal reflection fluorescence (TIRF) microscopy [2].
• The nucleotide sequence of BNPI predicts a protein of 560 amino acids with 6-8 putative transmembrane-spanning segments that is approximately 32% identical to the rabbit kidney Na(+)-dependent Pi cotransporter [3].
• Expression of BNPI mRNA in Xenopus oocytes results in Na(+)-dependent Pi transport similar to that reported for the recombinantly expressed or native kidney Na(+)-dependent cotransporter [3].
• RNA blot analysis reveals that BNPI mRNA is expressed predominantly (if not exclusively) in brain, and in situ hybridization histochemistry reveals BNPI transcripts in neurons of the cerebral cortex, hippocampus, and cerebellum [3].
• Because an enzyme known as the phosphate-activated glutaminase produces glutamate for release as a neurotransmitter, BNPI may augment excitatory transmission by increasing cytoplasmic phosphate concentrations within the nerve terminal and hence increasing glutamate synthesis [4].

Biological context of Slc17a7

• The results provide anatomic evidence of a specific presynaptic role for BNPI in glutamatergic neurotransmission, consistent with the phenotype of eat-4 mutants [4].
• As the abundance of VGLUT determines the quantal size, this up-regulation will increase excitatory postsynaptic currents (EPSCs) and have influences on synaptic physiology [5].

Anatomical context of Slc17a7

• Indirect immunocytochemistry showed a punctate pattern of VGLUT immunoreactivity throughout the entire cell body and processes, whereas pharmacological inhibition of VGLUTs abolished mechanically and agonist-evoked Ca2+-dependent glutamate release from astrocytes [6].
• Expression of BNPI on synaptic vesicles suggests a mechanism for neural activity to regulate the function of BNPI [4].
• Although BNPI depends on a Na+ gradient and presumably functions at the plasma membrane, both electron microscopy and biochemical fractionation show that BNPI associates preferentially with the membranes of small synaptic vesicles [4].
• VGLUT1, another VGLUT isoform, is also expressed and localized in secretory granules in alpha cells [7].
• Two subtypes of the vesicular glutamate transporter are expressed differentially in two excitatory afferents synapsing on to Purkinje cells: VGluT1 (BNPI) in axon terminals of cerebellar granule cells (i.e. parallel fibres; PFs) and VGluT2 (DNPI) in those of the inferior olivary neurons (climbing fibres; CFs) [8].

Associations of Slc17a7 with chemical compounds

• Zinc-positive boutons further immunoreacted to the vesicular glutamate transporter VGLUT-1, but not to the transmitter gamma-aminobutyric acid [9].
• However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2-immunoreactivity, or were not immunoreactive with either VGLUT antibody [10].
• These results suggest that endogenous L-glutamate could be released from intracellular vesicular constituents associated with BNPI through activation of particular iGluR subtypes expressed in cultured rat calvarial osteoblasts [11].

Regulatory relationships of Slc17a7

• At all ages, VGLUT immunoreactivity is localized to puncta that coexpress the presynaptic marker synaptophysin [12].

Other interactions of Slc17a7

• Changes in the transcripts of genes encoding 2 transporters [blood-brain specific anion transporter (Slco1c1) and sodium-dependent inorganic phosphate cotransporter (Slc17a7)] were confirmed by real-time RT-PCR [13].

Analytical, diagnostic and therapeutic context of Slc17a7

• Molecular cloning has recently identified a vertebrate brain-specific Na+-dependent inorganic phosphate transporter (BNPI) [4].

References