Normal Function
The SLC1A3 gene provides instructions for making a protein called excitatory amino acid transporter 1 (EAAT1). The EAAT1 protein is primarily found in nervous system cells called glia (or glial cells), which protect and maintain nerve cells (neurons). While the protein is found in cells throughout the brain, it is most abundant in the part of the brain that is connected to the spinal cord (the brainstem) and the region of the brain involved in coordinating movements (the cerebellum).
The EAAT1 protein transports a molecule called glutamate in the brain. Glutamate is one of several brain chemicals called neurotransmitters, which allow neurons to communicate with one another. EAAT1 also transports negatively charged chlorine atoms (chloride ions).
Neurotransmitters (such as glutamate) are released from neurons and relay signals to other cells by attaching to receptor proteins on neighboring neurons. After the neurotransmitters have had their effect, they detach from their receptors and must be cleared from the spaces between neurons. Researchers have determined that EAAT1 is one of several glutamate transporters that clear excess glutamate from these spaces. This process is carefully regulated to ensure that signals are transmitted accurately throughout the nervous system. The timely removal of glutamate is also necessary to prevent a buildup of this neurotransmitter between cells, which would be toxic to neurons.
The EAAT1 protein also transports chloride ions in and out of cells. This function of the protein may help regulate the size (volume) of glia by playing a role in their intake and release of water. EAAT1 may also help maintain a normal balance of charged molecules (ions) in cells.
Health Conditions Related to Genetic Changes
Episodic ataxia
Several variants (also called mutations) in the SLC1A3 gene have been found to cause episodic ataxia type 6 (EA6), which is a nervous system disorder involving episodes of poor coordination and balance (ataxia).
The variants that cause episodic ataxia change single protein building blocks (amino acids) in the EAAT1 protein. Research shows that the altered EAAT1 proteins allow more chloride ions to flow in or out of cells than usual. Researchers suspect that glia with these altered channels cannot maintain the correct volume or ion balance, causing them to shrink and die.
The loss of glia is thought to impair the clearance of glutamate from between neurons in the brain. The excess glutamate may overexcite certain neurons, disrupting normal communication between these cells. The changes in signaling between neurons likely causes the episodes of uncoordinated movement seen in people with episodic ataxia.
More About This Health ConditionOther Names for This Gene
- EA6
- EAA1_HUMAN
- EAAT-1
- EAAT1
- Excitatory amino acid transporter 1
- FLJ25094
- GLAST
- GLAST1
- Glial high affinity glutamate transporter
- Glutamate/aspartate transporter, high affinity, sodium-dependent
- Sodium-dependent glutamate/aspartate transporter 1
- solute carrier family 1 (glial high affinity glutamate transporter), member 3
- Solute carrier family 1 member 3
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Banner SJ, Fray AE, Ince PG, Steward M, Cookson MR, Shaw PJ. The expression of the glutamate re-uptake transporter excitatory amino acid transporter 1 (EAAT1) in the normal human CNS and in motor neurone disease: an immunohistochemical study. Neuroscience. 2002;109(1):27-44. doi: 10.1016/s0306-4522(01)00437-7. Citation on PubMed
- Beart PM, O'Shea RD. Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement. Br J Pharmacol. 2007 Jan;150(1):5-17. doi: 10.1038/sj.bjp.0706949. Epub 2006 Nov 6. Citation on PubMed or Free article on PubMed Central
- Chen I, Wu Q, Font J, Ryan RM. The twisting elevator mechanism of glutamate transporters reveals the structural basis for the dual transport-channel functions. Curr Opin Struct Biol. 2022 Aug;75:102405. doi: 10.1016/j.sbi.2022.102405. Epub 2022 Jun 13. Citation on PubMed
- Colucci E, Anshari ZR, Patino-Ruiz MF, Nemchinova M, Whittaker J, Slotboom DJ, Guskov A. Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6. Nat Commun. 2023 Mar 31;14(1):1799. doi: 10.1038/s41467-023-37503-y. Citation on PubMed
- Jen JC, Wan J, Palos TP, Howard BD, Baloh RW. Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures. Neurology. 2005 Aug 23;65(4):529-34. doi: 10.1212/01.wnl.0000172638.58172.5a. Citation on PubMed
- Kawakami H, Tanaka K, Nakayama T, Inoue K, Nakamura S. Cloning and expression of a human glutamate transporter. Biochem Biophys Res Commun. 1994 Feb 28;199(1):171-6. doi: 10.1006/bbrc.1994.1210. Citation on PubMed
- Kovermann P, Untiet V, Kolobkova Y, Engels M, Baader S, Schilling K, Fahlke C. Increased glutamate transporter-associated anion currents cause glial apoptosis in episodic ataxia 6. Brain Commun. 2020 Mar 4;2(1):fcaa022. doi: 10.1093/braincomms/fcaa022. eCollection 2020. Citation on PubMed
- Matsugami TR, Tanemura K, Mieda M, Nakatomi R, Yamada K, Kondo T, Ogawa M, Obata K, Watanabe M, Hashikawa T, Tanaka K. From the Cover: Indispensability of the glutamate transporters GLAST and GLT1 to brain development. Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12161-6. doi: 10.1073/pnas.0509144103. Epub 2006 Jul 31. Citation on PubMed or Free article on PubMed Central
- Stoffel W, Sasse J, Duker M, Muller R, Hofmann K, Fink T, Lichter P. Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12. FEBS Lett. 1996 May 20;386(2-3):189-93. doi: 10.1016/0014-5793(96)00424-3. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.