Reactome | SLC1A1,2,3,6,7 cotransport L-Glu,L-Asp,D-Asp,H+,3Na+ from extracellular region to cytosol

SLC1A1,2,3,6,7 cotransport L-Glu,L-Asp,D-Asp,H+,3Na+ from extracellular region to cytosol

Stable Identifier

R-HSA-428015

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

Synonyms

Glutamate transport

ReviewStatus

5/5

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SLC1A1,2,3,6,7 cotransport L-Glu,L-Asp,D-Asp,H+,3Na+ from extracellular region to cytosol

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There are two classes of glutamate transporters; the excitatory amino acid transporters (EAATs) which depend on an electrochemical gradient of Na+ ions and vesicular glutamate transporters (VGLUTs) which are proton-dependent. Together, these transporters uptake and release glutamate to mediate this neurotransmitter's excitatory signal and are part of the glutamate-gluatamine cycle.

The SLC1 gene family includes five high-affinity glutamate transporters encoded by SLC1, 2, 3, 6 and 7. These transporters can mediate transport of L-Glutamate, L-Aspartate and D-Aspartate with cotransport of 3 Na+ ions and H+ and antiport of a K+ ion. This mechanism allows glutamate into cells against a concentration gradient. This is a crucial factor in the protection of neurons against glutamate excitotoxicity in the CNS.

SLC1A1 encodes an excitatory amino-acid carrier 1 (EAAC1, also called EAAT3) (Shashidharan et al. 1994, Arriza et al. 1994) and is abundant particularly in brain but also in liver, muscle, ovary, testis and in retinoblastoma cell lines. In the kidney, EAAC1 is present at apical membranes of proximal tubes. Defects in SLC1A1 are the cause of dicarboxylic aminoaciduria (glutamate-aspartate transport defect in the kidney and intestine). SLC1A2 encodes the glial-type high affinity glutamate transporter (GLT1, EAAT2) (Arriza et al. 1994). GLT1 is expressed mainly in the brain and is essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft.

SLC1A3 encodes a sodium-dependent glutamate/aspartate transporter 1 (GLAST1, EAAT1). It is particularly abundant in the cerebellum and, like GLT1, plays a role in terminating the postsynaptic action of glutamate (Arriza JL et al, 1994). Defects in SLC1A3 are the cause of episodic ataxia type 6 (EA6), characterized by episodic ataxia, seizures, migraine and alternating hemiplegia (Jen JC et al, 2005).

SLC1A6 encodes an excitatory amino-acid transporter 4 (EAAT4) (Fairman WA et al, 1995) and is predominantly expressed in cerebellar Purkinje cells. SLC1A7 encodes an excitatory amino acid transporter 5 (EAAT5, retinal glutamate transporter) (Arriza JL et al, 1997) which is highly expressed in the retina.

Literature References

PubMed ID	Title	Journal	Year
7521911	Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex Arriza, JL, Fairman, WA, Wadiche, JI, Murdoch, GH, Kavanaugh, MP, Amara, SG	J Neurosci	1994
9108121	Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance Arriza, JL, Eliasof, S, Kavanaugh, MP, Amara, SG	Proc Natl Acad Sci U S A	1997
7791878	An excitatory amino-acid transporter with properties of a ligand-gated chloride channel Fairman, WA, Vandenberg, RJ, Arriza, JL, Kavanaugh, MP, Amara, SG	Nature	1995
7859077	Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain Shashidharan, P, Huntley, GW, Meyer, T, Morrison, JH, Plaitakis, A	Brain Res	1994
16116111	Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures Jen, JC, Wan, J, Palos, TP, Howard, BD, Baloh, RW	Neurology	2005