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Solute carrier family 17 member 6 (SLC17A6), also known as vesicular glutamate transporter 2 (VGLUT2) is an encoded polytopic membrane protein comprising of cytoplasmic amino-terminal, trans-membrane domains, and a large hydrophilic loop between TM8 and TM9 on the intracellular side. SLC17A6 expression is primarily restricted to subcortical and brainstem glutamatergic neurons with the highest transcription and protein levels found in thalamus, hypothalamus, amygdala and various brain stem nuclei, spinal cord and cerebellar deep nuclei. This distribution is mainly antagonistic to VGLUT1, which predominates in the cerebral cortex as well as hippocampus and cerebellar cortex. SLC17A6 dysregulation has been implicated pathologically in schizophrenia, major depressive disorder, epilepsy, chronic pain and neurodegenerative diseases. Knockout of the gene coding for SLC17A6 in various regions such as subthalamic nucleus causes cell loss, structural disorganization, hyperlocomotion, and disrupted reward processing mouse models.
Fig. 1 Graphical summary of developmental alcohol-induced epigenetic defect.1
The roles of SLC17A6 are really multifunctional and involve a variety of domains in neurobiology and neuropathology:
The membrane-embedded topology of the transporter, its dependence upon an appropriate lipid environment for proper folding, and regulation by chloride and the proton electrochemical gradient complicate structural and functional investigations of SLC17A6. To overcome these difficulties, Creative Biolabs developed a custom SLC17A6 design platform for membrane protein research constructs, enabling structural biology, ligand-binding studies, transport research, and monoclonal antibody development for research applications. We use structural insights and codon-optimized gene synthesis in our engineering efforts to develop constructs suited to studies of VGLUT2-mediated vesicular glutamate transport and its regulatory mechanisms. The first step in every engagement is a technical consultation to design the protein construct based upon its intended research application. Specific construct formats, preparation conditions, and structural or functional validation strategies are determined according to individual project requirements.
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For reliable vesicular uptake assays, we require cellular models that present functional SLC17A6 at the plasma membrane or synaptic vesicle–like compartments for monoclonal antibody screening and compound modulation. Engineered SLC17A6 stable cell lines can be generated by Creative Biolabs using proprietary transduction and selection methods for more homogeneous, persistent transporter expression. We harness lentiviral delivery, transposon-mediated integration and targeted knock-in to provide a streamlined cell engineering platform facilitating accurate genetic control. Rigorous monoclonal selection followed by detailed phenotypic validation confirms clonal purity, surface and intracellular transporter density, as well as functional glutamate uptake activity for each line.
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We have End-to-End recombinant antibody discovery programs against cytosolic and conformational SLC17A6 epitopes. In addition to immunogen design, multi-platform selection and downstream engineering are all integral components of our antibody development pipeline, enabling us to provide binders with the specificity, affinity and developability profiles suited for research use. We use recombinant expression and clonal sequencing to remove the batch-to-batch variability present in classical polyclonal sera, giving you a renewable, fully characterized reagent.
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Creative Biolabs goes beyond catalog products and provides comprehensive discovery services in support of all SLC17A6 research needs:
No, our SLC17A6 portfolio is manufactured solely for research use only.
Yes, we developed stable lines with high cell surface SLC17A6 expression and localization in intracellular vesicular compartments confirmed by immunofluorescence assays (IF) and functional glutamate accumulate assays.
Yes, we validated some of the selected clones in paraformaldehyde-fixed brain cryosections as well as on archival paraffin-embedded specimens following antigen retrieval that showed a specific punctate staining which coincided with distributions previously described for synaptic boutons and axonal varicosities.
Yes, the immunogen consists of a conserved region across mammalian species which enables reproducibly detectable levels in human, mouse and rat brain preparations or neuronal cell lysates without requiring different species-specific reagents; in all formats.