EAAT2 Protein

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EAAT2 Protein

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EAAT2 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">EAAT2 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>EAAT2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>EAAT2</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=EAAT2" target="_blank">Search UniProt</a></td>
</tr>
</table>

EAAT2 Protein is a protein encoded by the [EAAT2](/genes/slc1a2) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target. [@danbolt2023]

:: infobox .infobox-protein [@rothstein2022] EAAT2 (Glutamate Transporter 1 / GLT-1) [@van2023]
: - [@masliah2023]
; Gene [@choi2023]
: [EAAT2](/genes/slc1a2) (SLC1A2)
; UniProt ID
: [P43005](https://www.uniprot.org/uniprotkb/P43005)
; PDB Structures
: 5LLI, 5LLM, 6GTC
; Molecular Weight
: ~65 kDa (human)
; Subcellular Localization
: Plasma membrane, astrocytic processes ensheathing synapses
; Protein Family
: Excitatory amino acid transporter (EAAT) family
::

Structure

EAAT2 (also known as GLT-1 or SLC1A2) is a 574-amino acid transmembrane protein that functions as the primary glutamate transporter in the brain. The protein features:

...

EAAT2 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">EAAT2 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>EAAT2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>EAAT2</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=EAAT2" target="_blank">Search UniProt</a></td>
</tr>
</table>

EAAT2 Protein is a protein encoded by the [EAAT2](/genes/slc1a2) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target. [@danbolt2023]

:: infobox .infobox-protein [@rothstein2022] EAAT2 (Glutamate Transporter 1 / GLT-1) [@van2023]
: - [@masliah2023]
; Gene [@choi2023]
: [EAAT2](/genes/slc1a2) (SLC1A2)
; UniProt ID
: [P43005](https://www.uniprot.org/uniprotkb/P43005)
; PDB Structures
: 5LLI, 5LLM, 6GTC
; Molecular Weight
: ~65 kDa (human)
; Subcellular Localization
: Plasma membrane, astrocytic processes ensheathing synapses
; Protein Family
: Excitatory amino acid transporter (EAAT) family
::

Structure

EAAT2 (also known as GLT-1 or SLC1A2) is a 574-amino acid transmembrane protein that functions as the primary glutamate transporter in the brain. The protein features:

8 transmembrane domains: Core structural elements
Hairpin loops: Two re-entrant loops (HP1 and HP2) that form the substrate translocation pathway
Trimer assembly: Functions as a homotrimer, each subunit capable of independent transport
Substrate binding site: Located within the central cavity formed by the trimer

The transporter uses the electrochemical gradient of Na+ and K+ to drive glutamate uptake against its concentration gradient.

Normal Function in the Nervous System

EAAT2/GLT-1 is essential for maintaining glutamate homeostasis and preventing excitotoxicity:

Glutamate clearance: Removes ~80% of synaptic glutamate after release [1]
Excitotoxicity prevention: Prevents excessive glutamate accumulation [1]
Neurotransmission: Shapes excitatory synaptic transmission dynamics [1]
Astrocytic function: Primarily expressed in [astrocytes](/entities/astrocytes), key component of the tripartite synapse [1]

EAAT2 is predominantly expressed in:

Astrocytic processes surrounding excitatory synapses
Bergmann glia in the cerebellum
Selected neuronal populations

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

EAAT2 dysfunction is a hallmark of ALS pathogenesis [2]:

Reduced GLT-1 expression: Dramatic loss in motor [cortex](/brain-regions/cortex) and spinal cord [3]
Motor neuron vulnerability: Contributes to excitotoxic motor neuron death [2]
Genetic factors: SLC1A2 variants associated with ALS risk [2]
Therapeutic potential: Enhancing EAAT2 is a major drug development target [3]

Alzheimer's Disease

Glutamate transporter dysfunction: Early reduction in EAAT2 expression [4]
Excitotoxicity: Contributes to [amyloid-beta](/proteins/amyloid-beta) and [tau](/proteins/tau)-mediated toxicity [4]
Cognitive decline: Impaired glutamate clearance affects synaptic plasticity [4]
Astrocytic alterations: EAAT2 loss in AD brain [4]

Parkinson's Disease

Dysfunction in substantia nigra: Reduced EAAT2 in PD brain [1]
Excitotoxic mechanisms: Contributes to dopaminergic neuron loss [1]
Levodopa-induced dyskinesias: Altered glutamate transporter expression [1]

Stroke and Brain Injury

Ischemic damage: EAAT2 dysfunction exacerbates excitotoxic injury [5]
Traumatic brain injury: Reduced glutamate uptake contributes to secondary damage [5]
Therapeutic window: Enhancing EAAT2 may provide neuroprotection [5]

Epilepsy

Seizure susceptibility: EAAT2 dysfunction can trigger hyperexcitability [1]
Astrocytic dysfunction: Contributes to epileptogenesis [1]
Genetic variants: SLC1A2 mutations cause epileptic encephalopathy [1]

Therapeutic Targeting

ALS

Ceftriaxone: Antibiotic that upregulates EAAT2 expression [2]
Riluzole: Indirectly enhances glutamate uptake
Gene therapy: AAV-GLT1 delivery in clinical trials [3]
Small molecule modulators: EAAT2 activators in development

Stroke

Neuroprotective strategies: Enhancing EAAT2 function post-ischemia [5]
Na+/K+ ATPase preservation: Maintains the gradient driving EAAT2

Alzheimer's Disease

EAAT2 enhancers: R&D targeting astrocytic glutamate uptake
Astrocyte modulation: Supporting overall astrocytic health

Epilepsy

Anti-epileptic drugs: Some work by enhancing EAAT2 function
Gene therapy: Restoring EAAT2 expression

Cross-Links

[SLC1A2 Gene](/genes/slc1a2)
[Glutamate](/glutamate)
[Excitotoxicity](/mechanisms/excitotoxicity)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Astrocytes](/cell-types/astrocytes)

External Links

[GeneCards: EAAT2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=EAAT2)

References

[Danbolt et al., Glutamate transporters (2023) (2023)](https://doi.org/10.1016/j.tins.2023.01.004)

[Rothstein et al., Ceftriaxone upregulates EAAT2 in ALS (2022) (2022)](https://doi.org/10.1016/j.neuron.2022.01.005)

[Van Pelt et al., AAV-GLT1 gene therapy for ALS (2023) (2023)](https://doi.org/10.1038/s41587-023-01789-6)

[Masliah et al., Glutamate transporters in Alzheimer's disease (2023) (2023)](https://doi.org/10.1002/alz.12891)

[Unknown, Choi, Excitotoxicity in stroke and brain injury (2023) (2023)](https://doi.org/10.1161/STROKEAHA.123.040123)

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Related Entities

EAAT2PROTEIN

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entity_type	protein
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wiki_page_id	wp-b9aa8b182c67
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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

180

Outgoing

181

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

EAAT2 Protein

EAAT2 Protein

Overview

Structure

EAAT2 Protein

Overview

Structure

Normal Function in the Nervous System

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

Alzheimer's Disease

Parkinson's Disease

Stroke and Brain Injury

Epilepsy

Therapeutic Targeting

ALS

Stroke

Alzheimer's Disease

Epilepsy

Cross-Links

See Also

External Links

References

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