¶ title: "SLC1A2 Protein"
description: "Excitatory amino acid transporter 2 (EAAT2/GLT-1) - primary glutamate transporter in the brain"
published: true
tags: kind:protein, section:proteins, state:published
editor: markdown
pageId: 3701
dateCreated: "2026-03-04T19:49:17.262Z"
dateUpdated: "2026-03-25T05:20:00.000Z"
refs:
robinson1999:
authors: Robinson et al.
title: "Glutamate transporter dysfunction in ALS and Alzheimer's disease"
year: 1999
pmid: "10496356"
shields2000:
authors: Shields et al.
title: "EAAT2 expression and glutamate uptake in ALS"
year: 2000
pmid: "10781075"
SLC1A2 (Solute Carrier Family 2 Member 2), also known as EAAT2 (Excitatory Amino Acid Transporter 2) or GLT-1 (Glutamate Transporter 1), is the primary glutamate transporter in the central nervous system. It is responsible for the vast majority of glutamate reuptake from the synaptic cleft, playing a critical role in preventing excitotoxicity—a key pathological mechanism in neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) [@robinson1999].
¶ Gene and Protein Structure
The SLC1A2 gene (ENSG00000106852) is located on chromosome 11p13 and encodes a protein of 574 amino acids. EAAT2 exists as a homotrimer in the plasma membrane, with each monomer forming a functional transporter unit.
EAAT2 operates as a sodium-dependent transporter:
- Binding: Glutamate binds to extracellular site with 3 Na+ ions
- Conformational change: Transporter undergoes outward-to-inward transition
- Release: Glutamate and Na+ released into cytoplasm
- Reset: Transporter returns to outward-facing state
Stoichiometry:
- 1 glutamate: 3 Na+: 1 H+ (counter-transport)
- 1 K+ (cotransport in opposite direction)
EAAT2 is essential for:
- Synaptic glutamate clearance: Removes ~80% of released glutamate
- Preventing spillover: Limits extrasynaptic glutamate diffusion
- Metabolic recycling: Facilitates glutamate-glutamine cycle
- Maintaining low baseline glutamate: Keeps extracellular glutamate at ~0.6 μM
EAAT2 dysfunction is a hallmark of ALS [@shields2000]:
Expression Changes
- 50-70% reduction in EAAT2 protein in ALS motor cortex and spinal cord
- Decreased EAAT2 mRNA in affected regions
Pathogenic Mechanisms
- Oxidative stress damages EAAT2 promoter
- TDP-43 pathology disrupts SLC1A2 transcription
- MicroRNA-mediated post-transcriptional repression
EAAT2 alterations contribute to AD pathophysiology:
- Decreased EAAT2 in hippocampus and cortex
- Reduced glutamate uptake capacity
- Colocalization with amyloid plaques
EAAT2 provides neuroprotection in PD:
- Impaired glutamate uptake in substantia nigra
- Reduced EAAT2 expression in PD models
- Excitotoxic contribution to dopaminergic neuron death
EAAT2 Upregulators
- Ceftriaxone: β-lactam antibiotic that increases EAAT2 expression
- Riluzole: Indirect EAAT2 enhancement
- AAV-GLT1 delivery to brain
- Viral vector-mediated EAAT2 overexpression
EAAT2/GLT-1 represents a critical therapeutic target for neurodegenerative diseases characterized by excitotoxicity.