Disease relevance of Slc32a1

• RT-PCR analysis revealed that the mVGAT gene was expressed at a high level in retinoic acid-treated P19 embryonal carcinoma cells, at a very low level in non-treated P19 cells, and not detectably expressed in Neuro-2a neuroblastoma cells [1].
• We show that inactivation of the vesicular inhibitory amino acid transporter (Viaat, VGAT) leads to embryonic lethality, an abdominal defect known as omphalocele, and a cleft palate [2].
• Also, in offspring from the maternal hypoxia group, the vesicular GABA transporter (VGAT)-IR was enhanced in the hippocampal CA1 and hilus regions [3].

High impact information on Slc32a1

• Loss of Viaat causes a drastic reduction of neurotransmitter release in both GABAergic and glycinergic neurons, indicating that glycinergic neurons do not express a separate vesicular glycine transporter [2].
• In the absence of Viaat, GABA-synthesizing enzymes are partially lost from presynaptic terminals [2].
• Since GABA and glycine compete for vesicular uptake, these data point to a close association of Viaat with GABA-synthesizing enzymes as a key factor in specifying GABAergic neuronal phenotypes [2].
• Biochemical studies demonstrated the impairment of gamma-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in mu3B-/- mice [4].
• Vesicular inhibitory amino acid transporter (VIAAT), which is responsible for the storage of GABA and glycine in neuronal synaptic vesicles, is believed to be responsible for the storage and secretion of GABA in beta-cells [5].

Biological context of Slc32a1

• We find that the mouse Viaat coding sequence is encoded by two exons spanning 5.3 kb [6].
• Analysis of the Viaat promoter indicates that a minimal promoter region containing a CG rich sequence is sufficient for efficient expression in neural stem and precursor cells [6].
• To further assess synaptic transmission in mammalian horizontal cells, we examined the subcellular distribution of VIAAT in mouse and human retina by confocal microscopy with specific cell markers [7].
• The mouse vesicular inhibitory amino acid transporter gene: expression during embryogenesis, analysis of its core promoter in neural stem cells and a reconsideration of its alternate splicing [6].
• One major transcription start site of the mVGAT gene is an A residue 209 bp upstream from the translational initiation site, as shown using the 5'-RACE method [1].

Anatomical context of Slc32a1

• Combined biochemical, immunohistochemical, and electronmicroscopical evidence indicated that VIAAT is specifically localized with glucagon-containing secretory granules in alpha-cells [5].
• In the present study, we investigated the precise localization of VIAAT in rat islets of Langerhans and clonal islet cells and found that it is present in alpha-cells, a minor population of F-cells and alphaTC6 cells, and clonal alpha-cells but not in beta-cells, delta-cells, or MIN6 m9-cells (clonal beta-cells) [5].
• These differences between human retinal tissue and cultured cells were attributed to VIAAT degradation in postmortem retinal tissue [7].
• VIAAT localization in mouse and human horizontal cells further support the role of inhibitory transmitters in lateral inhibition at the photoreceptor terminals [7].
• VIAAT-positive puncta were also in apposition to lectin-labeled cone terminals or dendrites of PKCalpha-immunopositive rod bipolar cells, indicating that VIAAT is expressed in horizontal cell tips at both rod and cone terminals [7].

Associations of Slc32a1 with chemical compounds

• Results from immunoblotting showed that these drugs have similar effects on the expression of the GABA synthetic enzymes, glutamic acid decarboxylase65, glutamic acid decarboxylase67 and the vesicular GABA transporter [8].

Regulatory relationships of Slc32a1

• Deletion analysis and gel mobility shift assays demonstrated that the region -161 to +155 contained the basal promoter activity of the mVGAT gene and that an activating region from -49 to -27 bound an Sp1-like protein [1].

Other interactions of Slc32a1

• A survey of expression by whole mount in situ hybridization of mouse embryos indicates that Viaat is activated early in neuron differentiation and is expressed widely within the developing CNS; however, we did not detect expression in the superficial non-neural structures that express the GABA synthase Gad1 [6].
• Vesicular inhibitory amino acid transporter is present in glucagon-containing secretory granules in alphaTC6 cells, mouse clonal alpha-cells, and alpha-cells of islets of Langerhans [5].
• Immunocytochemistry and confocal microscopy were used for codetection of VIAAT, the common presynaptic vesicular transporter of glycine and GABA, GlyRs, GABA(A)R alpha1 and gamma2 subunits, and gephyrin, the scaffold protein implicated in the synaptic localization of inhibitory receptors [9].
• However, this rapid inhibition may not play a major role within local hypothalamic circuits, but rather is likely to be important in more distant projection areas as indicated by the colocalization of vesicular GABA transporter immunoreactivity predominantly in extrahypothalamic POMC terminals [10].
• Immunostaining with an antibody specific for the vesicular inhibitory amino acid transporter revealed that the number of inhibitory presynaptic terminals is unaltered upon gephyrin deficiency [11].

Analytical, diagnostic and therapeutic context of Slc32a1

• Fluorescent in situ hybridization studies showed that the mVGAT gene is localized on chromosome 2 [1].

References