SLC1A3

Solute carrier family 1 (glial high affinity glutamate transporter), member 3
Identifiers
Symbols	SLC1A3 ; EA6; EAAT1; GLAST; GLAST1
External IDs	OMIM: 600111 MGI: 99917 HomoloGene: 20882 ChEMBL: 3085 GeneCards: SLC1A3 Gene
Gene ontology
Molecular function	• L-glutamate transmembrane transporter activity; • high-affinity glutamate transmembrane transporter activity; • glutamate binding; • sodium:dicarboxylate symporter activity;
Cellular component	• mitochondrial inner membrane; • plasma membrane; • cell surface; • membrane; • integral component of membrane; • basolateral plasma membrane; • neuronal cell body; • dendritic spine; • fibril;
Biological process	• neurotransmitter uptake; • positive regulation of defense response to virus by host; • glutamate biosynthetic process; • ion transport; • synaptic transmission; • neurotransmitter secretion; • sensory perception of sound; • response to light stimulus; • gamma-aminobutyric acid biosynthetic process; • response to wounding; • glutamate secretion; • cranial nerve development; • auditory behavior; • response to drug; • malate-aspartate shuttle; • response to antibiotic; • cell morphogenesis involved in neuron differentiation; • positive regulation of synaptic transmission; • neuromuscular process controlling balance; • L-glutamate import; • transmembrane transport; • D-aspartate import; • L-glutamate transmembrane transport; • activation of mitophagy in response to mitochondrial depolarization;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

excitatory amino acid transporter 1

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/18 12:17:55」(JST)

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Solute carrier family 1 (glial high-affinity glutamate transporter), member 3, also known as SLC1A3,is a protein that, in humans, is encoded by the SLC1A3 gene.^[1] SLC1A3 is also often called the GLutamate ASpartate Transporter (GLAST) or Excitatory Amino Acid Transporter 1 (EAAT1) .

GLAST is predominantly expressed in the plasma membrane, allowing it to remove glutamate from the extracellular space.^[2] It has also been localized in the inner mitochondrial membrane as part of the malate-aspartate shuttle.^[3]

Mechanism

GLAST functions in vivo as a homotrimer.^[4] GLAST mediates the transport of glutamic and aspartic acid with the cotransport of three Na⁺ and one H⁺ cations and counter transport of one K⁺ cation. This co-transport coupling (or symport) allows the transport of glutamate into cells against a concentration gradient.^[5]

"Diagram Illustrating the Malate-Asparate Shuttle Pathway". (Glutamate aspartate transporter labeled at bottom center.)

Expression of SLC1A3 in the Bergmann glia fibers. Mouse brain at 7th postnatal day, sagittal section; GENSAT database.

Tissue distribution

GLAST is expressed throughout the CNS,^[6] and is highly expressed in astrocytes and Bergmann glia in the cerebellum.^[7]^[8] In the retina, GLAST is expressed in Muller cells.^[9] GLAST is also expressed in a number of other tissues including cardiac myocytes.^[3]

Clinical significance

It is associated with type 6 episodic_ataxia.^[10]

Pharmacology

DL-threo-beta-benzyloxyaspartate (TBOA) is an inhibitor of the excitatory amino acid transporters.^[11]

Selective inhibitors for GLAST 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.^[12]

References

^ "Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3".
^ Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC (March 1995). "Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations.". The Journal of neuroscience : the official journal of the Society for Neuroscience 15 (3 Pt 1): 1835–53. PMID 7891138.
^ ^a ^b Ralphe JC, Segar JL, Schutte BC, Scholz TD (2004). "Localization and function of the brain excitatory amino acid transporter type 1 in cardiac mitochondria". J. Mol. Cell. Cardiol. 37 (1): 33–41. doi:10.1016/j.yjmcc.2004.04.008. PMID 15242733.
^ Gendreau S, Voswinkel S, Torres-Salazar D, Lang N, Heidtmann H, Detro-Dassen S, Schmalzing G, Hidalgo P, Fahlke C (Sep 17, 2004). "A trimeric quaternary structure is conserved in bacterial and human glutamate transporters.". The Journal of Biological Chemistry 279 (38): 39505–12. doi:10.1074/jbc.M408038200. PMID 15265858.
^ Kanai Y, Hediger MA (2004). "The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects". Pflugers Arch. 447 (5): 469–79. doi:10.1007/s00424-003-1146-4. PMID 14530974.
^ Danbolt NC (September 2001). "Glutamate uptake". Prog. Neurobiol. 65 (1): 1–105. doi:10.1016/S0301-0082(00)00067-8. PMID 11369436.
^ Storck T, Schulte S, Hofmann K, Stoffel W (1992). "Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain". Proc. Natl. Acad. Sci. U.S.A. 89 (22): 10955–9. doi:10.1073/pnas.89.22.10955. PMC 50461. PMID 1279699.
^ Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (1994). "Localization of neuronal and glial glutamate transporters". Neuron 13 (3): 713–25. doi:10.1016/0896-6273(94)90038-8. PMID 7917301.
^ Rauen T, Taylor WR, Kuhlbrodt K, Wiessner M (1998). "High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance". Cell Tissue Res. 291 (1): 19–31. doi:10.1007/s004410050976. PMID 9394040.
^ Jen JC, Wan J, Palos TP, Howard BD, Baloh RW (2005). "Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures". Neurology 65 (4): 529–34. doi:10.1212/01.WNL.0000172638.58172.5a. PMID 16116111.
^ Shimamoto K, Lebrun B, Yasuda-Kamatani Y, Sakaitani M, Shigeri Y, Yumoto N, Nakajima T (February 1998). "DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters.". Molecular Pharmacology 53 (2): 195–201. PMID 9463476.
^ Jensen AA, Erichsen MN, Nielsen CW, Stensbøl TB, Kehler J, Bunch L (Feb 26, 2009). "Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1.". Journal of Medical Chemistry 52 (4): 912–5. doi:10.1021/jm8013458. PMID 19161278.

External links

Glutamate Aspartate Transporter 1 at the US National Library of Medicine Medical Subject Headings (MeSH)

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Related Pictures

File:PBB GE SLC1A3 202800 at tn.png Immunohistochemistry: SLC1A3 Antibody Expression of SLC1A3 in the Bergmann glia : SLC1A3 Antibody [NB100-1869] - SLC1A3 slc1a3 10941 cards entrez gene ncbi slc1a3 Flow (Intracellular): EAAT1/GLAST-1/SLC1A3 Description PBB GE SLC1A3 202800 at fs.png Slc1a3 Antibody | Excitatory amino acid