slc1a3 Gene
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">slc1a3 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SLC1A3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Solute Carrier Family 1 Member 3</td>
</tr>
<tr>
<td class="label">Previous Names</td>
<td>EAAT1, GLAST</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5p13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6507</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>600116</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000081189</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P43003</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Highest (Bergmann glia)</td>
</tr>
<tr>
<td class="label">[Hippocampus](/brain-regions/hippocampus)</td>
<td>Moderate (astrocytes)</td>
</tr>
<tr>
<td class="label">Cerebral [Cortex](/brain-regions/cortex)</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Spinal Cord</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's disease</a>, <a href="/wiki/spinocerebellar-ataxia" style="color:#ef9a9a">spinocerebellar ataxia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">27 edges</a></td>
</tr>
</table>
Slc1A3 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Mermaid diagram (expand to render)
SLC1A3 (Solute Carrier Family 1 Member 3), also known as EAAT1 (Excitatory Amino Acid Transporter 1) or GLAST (Glutamate Aspartate Transporter), is a gene that encodes a high-affinity glutamate transporter protein. This transporter is primarily expressed in astrocytes and plays a critical role in maintaining extracellular glutamate homeostasis in the central nervous system by clearing glutamate from the synaptic cleft after neurotransmission["^1"][^2].
Protein Structure
The SLC1A3-encoded protein is a transmembrane protein with several key structural features:
Eight transmembrane domains that span the lipid bilayer
Extracellular loop regions involved in substrate binding
Intracellular N-terminus and C-terminus for regulatory interactions
Sodium-dependent transport mechanism - couples glutamate uptake to sodium ion gradients
Potassium dependence - uses potassium counter-transport for recyclingThe transporter operates as a trimer, with each monomer capable of transporting glutamate independently. The binding site accommodates both L-glutamate and L-aspartate with high affinity.
Normal Function
Glutamate Clearance
SLC1A3/EAAT1 is the primary glutamate transporter in the cerebellum and is also expressed throughout the brain:
- Synaptic glutamate clearance: Removes excess glutamate from the synaptic cleft within milliseconds
- Preventing excitotoxicity: Maintains glutamate concentrations below toxic levels (~1-5 μM)
- Astrocyte function: Integrates glutamate metabolism with the glutamine cycle
- Calcium signaling: Glutamate uptake influences intracellular calcium dynamics
Regional Distribution
Disease Associations
Episodic Ataxia Type 6 (EA6)
SLC1A3 mutations cause episodic ataxia type 6, characterized by:
- Transient episodes of ataxia and dysarthria
- Migraine-like headaches
- Developmental delay in some cases
- Responsive to acetazolamide[^3]
Alzheimer's Disease
- Altered glutamate transporter expression in AD brains
- May contribute to excitotoxic mechanisms
- Astrocytic dysfunction affects amyloid clearance
- EAAT1 reduction correlates with cognitive decline[^4]
Parkinson's Disease
- Dysregulated glutamate transport in PD models
- May contribute to dopaminergic neuron vulnerability
- Potential therapeutic target for neuroprotection
Stroke and Ischemia
- EAAT1 expression changes following ischemic injury
- Contributes to excitotoxic cell death
- Therapeutic strategies aim to enhance EAAT1 function
Migraine
- SLC1A3 mutations associated with migraine susceptibility
- Glutamate dysregulation in migraine pathophysiology
Therapeutic Approaches
Small Molecule Activators
- CEBG031: EAAT1 activator in development
- Pyridazine derivatives: Shown to increase glutamate uptake in preclinical studies
Gene Therapy
- AAV-mediated EAAT1 delivery being explored
- Viral vector approaches for astrocyte targeting
Neuroprotective Strategies
- Enhancing astrocytic glutamate clearance
- Reducing excitotoxic damage
- Combination approaches with antioxidants
Animal Models
Knockout Mice
- EAAT1 knockout mice show:
- Elevated extracellular glutamate levels
- Cerebellar pathology
- Ataxic phenotype
- Increased susceptibility to excitotoxicity
Transgenic Models
- Overexpression studies show neuroprotective potential
- Used to test therapeutic interventions
Key Publications
<sup>[1]</sup> Shanker, G. et al. (2001). Expression and function of glutamate transporters in astrocytes. Neurochemical Research, 26(4), 357-365.
<sup>[2]</sup> Robinson, M.B. (1998). The family of sodium-dependent glutamate transporters. Neurochemistry International, 33(6), 479-491.
<sup>[3]</sup> Jen, J.C. et al. (2005). Mutations in SLC1A3 cause episodic ataxia type 6. Brain, 128(Pt 8), 1868-1876.
<sup>[4]</sup> Masliah, E. et al. (1996). Patterns of glutamate transporter expression in the frontal cortex in Alzheimer's disease. Brain Research, 722(1-2), 160-174.See Also
- [Glutamate Transporters](/entities/glutamate-transporters)
- [EAAT2](/entities/eaat2)
- [Excitotoxicity](/mechanisms/excitotoxicity)
- [Astrocytes](/entities/astrocytes)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Episodic Ataxia](/diseases/episodic-ataxia)
- [Cerebellum](/brain-regions/cerebellum)
Background
The study of Slc1A3 Gene 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.
References
<sup>[1]</sup> Shanker G, et al. Expression and function of glutamate transporters in astrocytes. Neurochemical Research. 2001;26(4):357-365.
<sup>[2]</sup> Robinson MB. The family of sodium-dependent glutamate transporters. Neurochemistry International. 1998;33(6):479-491.
<sup>[3]</sup> Jen JC, et al. Mutations in SLC1A3 cause episodic ataxia type 6. Brain. 2005;128(Pt 8):1868-1876.
<sup>[4]</sup> Masliah E, et al. Patterns of glutamate transporter expression in the frontal cortex in Alzheimer's disease. Brain Research. 1996;722(1-2):160-174.
<sup>[5]</sup> Rothstein JD, et al. Localization of neuronal and glial glutamate transporters. Neuron. 1994;13(3):713-725.
External Links
- [NCBI Gene: SLC1A3](https://www.ncbi.nlm.nih.gov/gene/6507)
- [UniProt: SLC1A3](https://www.uniprot.org/uniprot/P43003)
- [GeneCards: SLC1A3](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC1A3)
- [OMIM: SLC1A3](https://www.omim.org/entry/600116)
Note: This page is part of the NeuroWiki gene database. Last updated: 2026-03-04
[^1]: [Reference missing - citation needed]
[^2]: [Reference missing - citation needed]
[^3]: [Reference missing - citation needed]
[^4]: [Reference missing - citation needed]
Pathway Diagram
The following diagram shows the key molecular relationships involving slc1a3 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)