VGAT Protein

VGAT Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">VGAT Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>VGAT</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>VGAT</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=VGAT" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

VGAT Protein is a protein encoded by the [SLC32A1](/genes/slc32a1) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

:: infobox .infobox-protein [@martens2023] VGAT (Vesicular GABA Transporter) [@wagner2023]
: - [@brown2023]
; Gene [@li2023]
: [SLC32A1](/genes/slc32a1) [@zhang2023]
; UniProt ID
: [Q9H1H4](https://www.uniprot.org/uniprotkb/Q9H1H4)
; PDB Structures
: 5VSL, 5VSM
; Molecular Weight
: ~57 kDa (human)
; Subcellular Localization
: Synaptic vesicles of GABAergic and glycinergic [neurons](/entities/neurons)
; Protein Family
: Vesicular inhibitory amino acid transporter (VIAAT) family
::

Structure

VGAT (SLC32A1), also known as VIAAT (Vesicular Inhibitory Amino Acid Transporter), is a 525-amino acid transmembrane protein that packages GABA and glycine into synaptic vesicles. The protein features:

VGAT Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">VGAT Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>VGAT</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>VGAT</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=VGAT" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

VGAT Protein is a protein encoded by the [SLC32A1](/genes/slc32a1) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

:: infobox .infobox-protein [@martens2023] VGAT (Vesicular GABA Transporter) [@wagner2023]
: - [@brown2023]
; Gene [@li2023]
: [SLC32A1](/genes/slc32a1) [@zhang2023]
; UniProt ID
: [Q9H1H4](https://www.uniprot.org/uniprotkb/Q9H1H4)
; PDB Structures
: 5VSL, 5VSM
; Molecular Weight
: ~57 kDa (human)
; Subcellular Localization
: Synaptic vesicles of GABAergic and glycinergic [neurons](/entities/neurons)
; Protein Family
: Vesicular inhibitory amino acid transporter (VIAAT) family
::

Structure

VGAT (SLC32A1), also known as VIAAT (Vesicular Inhibitory Amino Acid Transporter), is a 525-amino acid transmembrane protein that packages GABA and glycine into synaptic vesicles. The protein features:

• 10 transmembrane domains: Characteristic of the SLC family
• Vesicular lumen orientation: Transports inhibitory amino acids into vesicles
• Proton gradient coupling: Uses V-ATPase-generated H+ gradient
• Functional homodimer: Forms functional dimers for transport

Normal Function in the Nervous System

VGAT is essential for inhibitory neurotransmission:

• GABA packaging: Packages GABA into synaptic vesicles [1]
• Glycine packaging: Also transports glycine in spinal cord and brainstem [1]
• Inhibitory transmission: Critical for fast synaptic inhibition [1]
• Network regulation: Controls excitatory/inhibitory balance [1]

• GABAergic cortical interneurons
• Cerebellar Purkinje cells
• Spinal cord glycinergic neurons
• Brainstem inhibitory neurons

Role in Disease

Epilepsy

VGAT dysfunction is implicated in epilepsy [2]:

• Reduced inhibitory transmission: Diminished GABA release [3]
• Network hyperexcitability: Contributes to seizure generation [2]
• Genetic factors: SLC32A1 mutations cause epilepsy [2]
• Therapeutic targeting: Enhancing VGAT function [3]

Alzheimer's Disease

• Inhibitory dysfunction: Altered VGAT expression in AD [4]
• Network imbalance: Excitatory/inhibitory ratio affected [4]
• Cognitive decline: Contributes to circuit dysfunction [4]

Parkinson's Disease

• Basal ganglia dysfunction: VGAT in striatal interneurons [1]
• Motor control: Altered inhibition affects movement [1]
• Dyskinesias: GABAergic dysfunction in LIDs [1]

Huntington's Disease

• GABAergic loss: Early loss of VGAT-positive neurons [5]
• Striatal degeneration: Contributes to motor symptoms [5]
• Network alterations: Affects cortico-striatal circuits [5]

Schizophrenia

• GABAergic deficit: Altered VGAT expression in prefrontal [cortex](/brain-regions/cortex) [1]
• Cognitive dysfunction: Affects working memory circuits [1]

Therapeutic Targeting

Epilepsy

• VGAT enhancers: Experimental approaches to boost GABA packaging
• Gene therapy: Restoring VGAT expression

Neurodegeneration

• Inhibitory modulation: Restoring excitatory/inhibitory balance
• Combination approaches: With other therapeutic targets

Research Tools

• VGAT-Cre mice: Genetic access to inhibitory neurons
• VGAT-GFP reporters: Visualization of inhibitory neurons

Cross-Links

• [SLC32A1 Gene](/genes/slc32a1)
• [GABA](/biochemistry/neurotransmitters/gaba)
• [Glycine](/biochemistry/neurotransmitters/glycine)
• [Epilepsy](/diseases/epilepsy)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Inhibitory Transmission](/mechanisms/inhibitory-transmission)

Pathway & Interaction Diagram

Interactive diagram showing VGAT's key relationships in the SciDEX knowledge graph (7 connections shown).

See Also

• [SLC32A1 Gene](/genes/slc32a1)
• [Epilepsy](/diseases/epilepsy)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Inhibitory Transmission](/mechanisms/inhibitory-transmission)

External Links

• [GeneCards: SLC32A1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC32A1)

References