Excitatory amino acid transporter 1 (EAAT1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that, in humans, is encoded by the ''SLC1A3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1). EAAT1 is predominantly expressed in the plasma membrane, allowing it to remove glutamate from the extracellular space. It has also been localized in the inner mitochondrial membrane as part of the

malate-aspartate shuttle The malate-aspartate shuttle (sometimes simply the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryo ...

Mechanism

EAAT1 functions ''in vivo'' as a

homotrimer thumbnail, 400px, Trimeric form of a TNF-α mutant A homotrimer is a protein which is composed of three identical units of polypeptide. Examples * Hemagglutinin (influenza) * Spike protein (coronavirus) See also * Protein trimer In biochemi ...

. EAAT1 mediates the transport of glutamic and

aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...

with the

cotransport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

of three Na⁺ and one H⁺ cations and counter transport of one K⁺ cation. This co-transport coupling (or

symport A symporter is an integral membrane protein that is involved in the transport of two (or more) different molecules across the cell membrane in the same direction. The symporter works in the plasma membrane and molecules are transported across the ...

) allows the transport of glutamate into cells against a concentration gradient.

Tissue distribution

EAAT1 is expressed throughout the CNS, and is highly expressed in astrocytes and Bergmann glia in the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

. In the retina, EAAT1 is expressed in

Muller cell Muller is a surname. Notable people with the surname include: A–H * A. Charles Muller (born 1953), translator *Bauke Muller (born 1962), Dutch bridge player *Bennie Muller (born 1938), Dutch footballer *Bill Muller (1965–2007), US journalist ...

s. EAAT1 is also expressed in a number of other tissues including cardiac myocytes.

Clinical significance

It is associated with type 6

episodic ataxia Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognized but the majority are due to two recog ...

. EAAT1 expression may also be associated with

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

Pharmacology

DL-threo-beta-benzyloxyaspartate (TBOA) is an inhibitor of the excitatory amino acid transporters. Selective inhibitors for EAAT1 have recently been discovered based on 25 combinations of substitutions at the 4 and 7 positions of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitril.

References

External links