EAAT4 Protein (Excitatory Amino Acid Transporter 4)

Migration, Crosslink

📖

EAAT4 Protein (Excitatory Amino Acid Transporter 4)

active

wiki page Created: 2026-04-02T07:19:10 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-proteins-eaat4-protein

📖 Wiki Page

protein651 wordssynced 2026-04-02

EAAT4 Protein (Excitatory Amino Acid Transporter 4)

Overview

Eaat4 Protein (Excitatory Amino Acid Transporter 4) plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
PMID: 17182680

Introduction

Eaat4 Protein (Excitatory Amino Acid Transporter 4) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@ref1992]

<div class="infobox infobox-protein"> [@ref1994a]

EAAT4 [@ref2001]

| | |
|---|---|
| Protein Name | EAAT4 |
| Gene | [SLC1A6](/genes/slc1a6) |
| UniProt ID | [P22732](https://www.uniprot.org/uniprot/P22732) |
| Molecular Weight | ~65 kDa |
| Subcellular Localization | Plasma membrane (neurons) |
| Protein Family | SLC1 (EAAT) family |
| Associated Diseases | [Epilepsy](/diseases/epilepsy), [Ataxia](/diseases/ataxia), [Neurodegeneration](/diseases/neurodegeneration) |

</div>

Structure

EAAT4 is a transmembrane protein with:

Eight transmembrane domains
A reentrant loop between transmembrane domains 7 and 8
Intracellular N- and C-termini
Glycosylation sites in extracellular loops

...

EAAT4 Protein (Excitatory Amino Acid Transporter 4)

Overview

Eaat4 Protein (Excitatory Amino Acid Transporter 4) plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
PMID: 17182680

Introduction

Eaat4 Protein (Excitatory Amino Acid Transporter 4) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@ref1992]

<div class="infobox infobox-protein"> [@ref1994a]

EAAT4 [@ref2001]

| | |
|---|---|
| Protein Name | EAAT4 |
| Gene | [SLC1A6](/genes/slc1a6) |
| UniProt ID | [P22732](https://www.uniprot.org/uniprot/P22732) |
| Molecular Weight | ~65 kDa |
| Subcellular Localization | Plasma membrane (neurons) |
| Protein Family | SLC1 (EAAT) family |
| Associated Diseases | [Epilepsy](/diseases/epilepsy), [Ataxia](/diseases/ataxia), [Neurodegeneration](/diseases/neurodegeneration) |

</div>

Structure

EAAT4 is a transmembrane protein with:

Eight transmembrane domains
A reentrant loop between transmembrane domains 7 and 8
Intracellular N- and C-termini
Glycosylation sites in extracellular loops

The transporter has a "transport gate" mechanism where the substrate binding site is alternately exposed to the extracellular and intracellular sides. EAAT4 contains ankyrin-binding motifs in its C-terminal domain, allowing association with the cytoskeleton.
PMID: 20011524

Normal Function in the Nervous System

EAAT4 is a high-affinity glutamate transporter that:

Glutamate clearance: Removes glutamate from the extracellular space with high affinity (Km ~10 μM), preventing excitotoxic accumulation.

PMID: 11968459

Sodium coupling: Cotransports 3 Na+ and 1 H+ with each glutamate, countertransporting 1 K+. This electrogenic process contributes to the resting membrane potential.

PMID: 30537735

Anion channel activity: Unlike other EAATs, EAAT4 exhibits significant chloride conductance when activated, which may modulate neuronal excitability.

Spatial buffering: In Purkinje cells, EAAT4 helps buffer extracellular glutamate during parallel fiber-Purkinje cell synaptic transmission, shaping cerebellar plasticity.

EAAT4's unique properties make it crucial for:

Preventing cerebellar excitotoxicity
Modulating synaptic plasticity in the cerebellum
Protecting against ischemia and oxidative stress

Role in Disease

EAAT4 dysfunction contributes to neurological disorders:

Ataxia:

Impaired glutamate clearance in Purkinje cells leads to abnormal firing patterns
Disrupted cerebellar plasticity and motor learning deficits
Purkinje cell degeneration in some ataxic disorders

Epilepsy:

Reduced glutamate uptake promotes hyperexcitability
Aberrant burst firing in cerebellar circuits
Secondary excitotoxic damage

Neurodegeneration:

Chronic excitotoxicity due to impaired glutamate clearance
Accelerated neuronal death in stroke and traumatic brain injury
Possible contribution to Alzheimer's disease progression

Ischemia:

Energy failure leads to reversed EAAT4 operation
Release of glutamate instead of uptake
Excitotoxic cell death cascade

Therapeutic Targeting

Therapeutic strategies for EAAT4:

Positive allosteric modulators: Enhance EAAT4 transporter function to increase glutamate clearance.

Gene therapy: AAV-mediated EAAT4 overexpression in cerebellar [neurons](/entities/neurons).

Sodium channel modulators: Since EAAT4 is sodium-dependent, modulating sodium channels can indirectly affect glutamate transport.

Anti-epileptic drugs: Some AEDs may act partly through enhancing EAAT function.

Neuroprotective strategies: Targeting downstream excitotoxic pathways when EAAT4 function is compromised.

Key Publications

[UniProt Entry](https://www.uniprot.org/uniprot/P22732)

[NCBI Gene Entry](https://www.ncbi.nlm.nih.gov/gene/6512)

Cross-Links

[Gene: SLC1A6](/genes/slc1a6)
[Epilepsy](/diseases/epilepsy), [Ataxia](/diseases/ataxia), [Neurodegeneration](/diseases/neurodegeneration)

Overview

Eaat4 Protein (Excitatory Amino Acid Transporter 4) plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Background

The study of Eaat4 Protein (Excitatory Amino Acid Transporter 4) 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.

Pathway & Interaction Diagram

Interactive diagram showing EAAT4's key relationships in the SciDEX knowledge graph (5 connections shown).

Mermaid diagram (expand to render)

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

[Unknown, 7542809 (1994)](https://doi.org/10.1038/360467a0)

[Unknown, 8624976 (1992)](https://doi.org/10.1073/pnas.89.22.10955)

[Unknown, 11306659 (1994)](https://doi.org/10.1523/JNEUROSCI.14-09-05559.1994)

[Unknown, 14601077 (2001)](https://doi.org/10.1016/s0301-0082(00)

📖 View canonical wiki page →

Related Entities

EAAT4PROTEIN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-eaat4-protein
kg_node_id	EAAT4PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-d6bbe90c5973
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-eaat4-protein'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

25

Outgoing

27

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

EAAT4 Protein (Excitatory Amino Acid Transporter 4)

EAAT4 Protein (Excitatory Amino Acid Transporter 4)

Overview

Introduction

Structure

EAAT4 Protein (Excitatory Amino Acid Transporter 4)

Overview

Introduction

Structure

Normal Function in the Nervous System

Role in Disease

Therapeutic Targeting

Key Publications

Cross-Links

Overview

Background

Pathway & Interaction Diagram

See Also

External Links

References

💬 Discussion