Excitatory amino acid transporter 1

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Excitatory Amino Acid Transporter 1

Diagram of the malate-aspartate shuttle, which is related to the function of EAAT1.

Excitatory Amino Acid Transporter 1 (EAAT1) is a protein that in humans is encoded by the SLC1A3 gene. EAAT1 is a member of the solute carrier family and functions primarily as a glutamate transporter. It plays a crucial role in the regulation of glutamate levels in the central nervous system (CNS), thereby maintaining neurotransmitter balance and preventing excitotoxicity.

Function

EAAT1 is primarily expressed in astrocytes, a type of glial cell in the brain. It is responsible for the uptake of glutamate from the synaptic cleft, which is essential for terminating the excitatory signal of this neurotransmitter. By removing excess glutamate, EAAT1 helps to prevent excitotoxicity, a condition that can lead to neuronal damage and is implicated in various neurodegenerative disorders.

The transporter operates by coupling the transport of glutamate with the movement of other ions, such as sodium and potassium, across the cell membrane. This process is energy-dependent and relies on the electrochemical gradients of these ions.

Structure

EAAT1 is a transmembrane protein that spans the cell membrane multiple times. It belongs to the family of solute carrier proteins, specifically the SLC1 family. The structure of EAAT1 allows it to bind glutamate and co-transport ions, facilitating the movement of these molecules across the cell membrane.

Clinical Significance

Mutations in the SLC1A3 gene, which encodes EAAT1, have been associated with various neurological conditions. For example, certain mutations can lead to episodic ataxia, a disorder characterized by episodes of poor coordination and balance. Additionally, dysfunction of EAAT1 has been implicated in epilepsy, schizophrenia, and other neuropsychiatric disorders.

Research and Therapeutic Potential

Research into EAAT1 and its role in the CNS continues to be an area of active investigation. Understanding the precise mechanisms by which EAAT1 regulates glutamate levels could lead to new therapeutic strategies for treating neurodegenerative diseases and neuropsychiatric disorders.

Expression of SLC1A3 in Bergmann glia, highlighting the role of EAAT1 in the cerebellum.

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Contributors: Prab R. Tumpati, MD