Slc17A6 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| VGLUT2 | |
|---|---|
| Gene Symbol | SLC17A6 |
| UniProt ID | Q9P1U1 |
| PDB ID | 5W5U, 6E7K |
| Molecular Weight | 65.4 kDa |
| Subcellular Localization | Synaptic vesicle membrane, presynaptic terminal |
| Protein Family | SLC17 family (vesicular glutamate transporters) |
Vesicular Glutamate Transporter 2 (VGLUT2), encoded by the SLC17A6 gene, is a proton-coupled glutamate transporter that packages glutamate into synaptic vesicles[1]. VGLUT2 is the primary vesicular glutamate transporter in subpopulations of excitatory neurons throughout the brain, particularly in thalamus, brainstem, and subcortical structures. By mediating glutamate uptake into synaptic vesicles, VGLUT2 is essential for glutamatergic neurotransmission and is implicated in various neurological and neurodegenerative disorders.
VGLUT2 contains 12 transmembrane domains characteristic of the SLC17 family:
VGLUT2 uses a proton gradient to drive glutamate uptake[2]:
| Substrate | Affinity (Km) | Notes |
|---|---|---|
| L-Glutamate | ~0.3 mM | Primary substrate |
| L-Aspartate | ~2 mM | Minor substrate |
| N-Acetylaspartylglutamate | ~1 mM | Co-released |
VGLUT2 is essential for packing glutamate into synaptic vesicles[3]:
VGLUT2 is expressed in glutamatergic neurons:
| VGLUT | Primary Expression | Function |
|---|---|---|
| VGLUT1 | Cortex, hippocampus | Major cortical VGLUT |
| VGLUT2 | Thalamus, brainstem | Major subcortical VGLUT |
| VGLUT3 | Cholinergic, serotonergic | Non-classical VGLUT |
VGLUT2 alterations in AD[4]:
| Approach | Mechanism | Status |
|---|---|---|
| VGLUT2 inhibitors | Reduce glutamate release | Preclinical |
| Proton gradient modulators | Affect VGLUT2 activity | Research |
| Gene therapy | Modulate expression | Research |
The study of Slc17A6 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Shigeri Y, et al. (2004). Molecular pharmacology of glutamate transporters. Journal of Neurochemistry. 90(3):507-517.
[2] Schenck S, et al. (2009). The crystal structure of a eukaryotic vesicular glutamate transporter. Nature. 459(7244):347-355.
[3] Fremeau RT, et al. (2004). The expression of vesicular glutamate transporters defines excitatory neural circuits. Journal of Neuroscience. 24(10):2517-2530.
[4] Li S, et al. (2020). Vesicular glutamate transporter in Alzheimer's disease. Neurobiology of Aging. 90:43-52.