SLC1A1

Last updated
SLC1A1
Identifiers
Aliases SLC1A1 , EAAC1, EAAT3, SCZD18, DCBXA, solute carrier family 1 member 1
External IDs MGI: 105083 HomoloGene: 20881 GeneCards: SLC1A1
Gene location (Human)
Ideogram human chromosome 9.svg
Chr. Chromosome 9 (human) [1]
Human chromosome 9 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 9p24.2Start4,490,468 bp [1]
End4,587,469 bp [1]
RNA expression pattern
PBB GE SLC1A1 206396 at fs.png

PBB GE SLC1A1 213664 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

6505

20510

Ensembl

ENSG00000106688

ENSMUSG00000024935

UniProt

P43005

P51906

RefSeq (mRNA)

NM_004170

NM_009199

RefSeq (protein)

NP_004161

NP_033225

Location (UCSC) Chr 9: 4.49 – 4.59 Mb Chr 19: 28.84 – 28.91 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Excitatory amino acid transporter 3 (EAAT3), is a protein that in humans is encoded by the SLC1A1 gene. [5] [6]

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

Gene Basic physical and functional unit of heredity

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

Contents

Tissue distribution

EAAT3 is expressed on the plasma membrane of neurons, specifically on the dendrites and axon terminals. [7]

Axon terminal Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal bouton is a specialized region of it.

Axon terminals are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses called action potentials away from the neuron's cell body, or soma, in order to transmit those impulses to other neurons, muscle cells or glands.

Function

Excitatory amino acid transporter 3 is a member of the high-affinity glutamate transporters which plays an essential role in transporting glutamate across plasma membranes in neurons. In the brain, excitatory amino acid transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. EAAT3 also transports aspartate, and mutations in this gene are thought to cause dicarboxylic aminoaciduria, also known as glutamate-aspartate transport defect. [6] EAAT3 is also the major route of neuronal cysteine uptake. Cysteine is a component of the major antioxidant glutathione, and mice lacking EAAT3 exhibit reduced levels of glutathione in neurons, increased oxidative stress, and age-dependent loss of neurons, especially neurons of the substantia nigra.

Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons, while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate.

Neuron electrically excitable cell

A neuron, also known as a neurone or nerve cell, is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue. All animals except sponges and placozoans have neurons, but other multicellular organisms such as plants do not.

Neurotransmitter endogenous chemicals that transmit signals across a synapse from one neuron to another

Neurotransmitters are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron to another "target" neuron, muscle cell, or gland cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are readily available from the diet and only require a small number of biosynthetic steps for conversion. Neurotransmitters play a major role in shaping everyday life and functions. Their exact numbers are unknown, but more than 200 chemical messengers have been uniquely identified.

Interactions

SLC1A1 has been shown to interact with ARL6IP5. [8]

See also

The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 65 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO Gene Nomenclature Committee (HGNC) and is the basis for the official HGNC names of the genes that encode these transporters. A more general transmembrane transporter classification can be found in TCDB database.

Related Research Articles

Glutamate receptor

Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.

Excitatory amino acid transporter 5 protein-coding gene in the species Homo sapiens

Excitatory amino-acid transporter 5 (EAAT5) is a protein that in humans is encoded by the SLC1A7 gene.

Excitatory amino acid transporter 4 protein-coding gene in the species Homo sapiens

Excitatory amino-acid transporter 4 (EAAT4) is a protein that in humans is encoded by the SLC1A6 gene.

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.

Glutamate aspartate transporter protein-coding gene in the species Homo sapiens

Excitatory amino acid transporter 1 (EAAT1) is a protein that, in humans, is encoded by the SLC1A3 gene. EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1).

SLC1A2 protein-coding gene in the species Homo sapiens

Excitatory amino acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) and glutamate transporter 1 (GLT-1) is a protein that in humans is encoded by the SLC1A2 gene. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

GRIA2 protein-coding gene in the species Homo sapiens

Glutamate ionotropic receptor AMPA type subunit 2 is a protein that in humans is encoded by the GRIA2 gene.

ARL6IP5 protein-coding gene in the species Homo sapiens

PRA1 family protein 3 is a protein that in humans is encoded by the ARL6IP5 gene.

GRIN3A protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit 3A is a protein that in humans is encoded by the GRIN3A gene.

GRIN2D protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit epsilon-4 is a protein that in humans is encoded by the GRIN2D gene.

GRIN3B protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit 3B is a protein that in humans is encoded by the GRIN3B gene.

Cystine/glutamate transporter

Cystine/glutamate transporter is an antiporter that in humans is encoded by the SLC7A11 gene.

An Error has occurred retrieving Wikidata item for infobox Neutral amino acid transporter A is a protein that in humans is encoded by the SLC1A4 gene.

Cationic amino acid transporter 3 protein-coding gene in the species Homo sapiens

Cationic amino acid transporter 3 is a protein that in humans is encoded by the SLC7A3 gene.

Plasma membrane monoamine transporter protein-coding gene in the species Homo sapiens

The plasma membrane monoamine transporter (PMAT) is a low-affinity monoamine transporter protein which in humans is encoded by the SLC29A4 gene. It is known alternatively as the human equilibrative nucleoside transporter-4 (hENT4). Unlike other members of the ENT family, it is impermeable to most nucleosides, with the exception of the inhibitory neurotransmitter and ribonucleoside adenosine, which it is permeable to in a highly pH-dependent manner.

WAY-213,613 chemical compound

WAY-213,613 is a drug which acts as a reuptake inhibitor for the glutamate transporter subtype EAAT2, selective over other glutamate transporter subtypes and highly selective over metabotropic and ionotropic glutamate receptors. It is used in scientific research into the function of the glutamate transporters.

Sodium-dependent neutral amino acid transporter B(0)AT2 protein-coding gene in the species Homo sapiens

Sodium-dependent neutral amino acid transporter B(0)AT2 is a protein that in humans is encoded by the SLC6A15 gene.

Dicarboxylic aminoaciduria is a rare form of aminoaciduria which is an autosomal recessive disorder of urinary glutamate and aspartate due to genetic errors related to transport of these amino acids. Mutations resulting in a lack of expression of the SLC1A1 gene, a member of the solute carrier family, are found to cause development of dicarboxylic aminoaciduria in humans. SLC1A1 encodes for EAAT3 which is found in the neurons, intestine, kidney, lung, and heart. EAAT3 is part of a family of high affinity glutamate transporters which transport both glutamate and aspartate across the plasma membrane.

An excitatory amino acid reuptake inhibitor (EAARI) is a type of drug which inhibits the reuptake of the excitatory neurotransmitters glutamate and aspartate by blocking one or more of the excitatory amino acid transporters (EAATs).

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000106688 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024935 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ Smith CP, Weremowicz S, Kanai Y, Stelzner M, Morton CC, Hediger MA (August 1994). "Assignment of the gene coding for the human high-affinity glutamate transporter EAAC1 to 9p24: potential role in dicarboxylic aminoaciduria and neurodegenerative disorders". Genomics. 20 (2): 335–6. doi:10.1006/geno.1994.1183. PMID   8020993.
  6. 1 2 "Entrez Gene: SLC1A1 solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1".
  7. ↑ Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG (July 2014). "Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons". Neuron. 83 (2): 404–16. doi:10.1016/j.neuron.2014.05.043. PMC   4159050 . PMID   25033183. In general, EAATs 1 and 2 are found predominantly in astrocytes, EAAT3 in neurons, EAAT4 in Purkinje cells, and EAAT5 expression is restricted to the retina (Danbolt, 2001). The dependence of EAAT3 internalization on the DAT also suggests that the two transporters might be internalized together. We found that EAAT3 and DAT are expressed in the same cells, as well as in axons and dendrites. However, the subcellular co-localization of the two neurotransmitter transporters remains to be established definitively by high resolution electron microscopy.
  8. ↑ Lin CI, Orlov I, Ruggiero AM, Dykes-Hoberg M, Lee A, Jackson M, Rothstein JD (2001). "Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18". Nature. 410 (6824): 84–8. doi:10.1038/35065084. PMID   11242046.

Further reading

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Huda Zoghbi Lebanese scientist

Huda Yahya Zoghbi, born Huda El-Hibri, is a Lebanese-born American geneticist, and a professor at the Department of Molecular and Human Genetics, Baylor College of Medicine. Her work helped elucidate mechanisms of Rett syndrome and spinocerebellar ataxia type 1. In 2017, she was awarded the Canada Gairdner International Award and the Breakthrough Prize in Life Sciences.

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