L-穀氨酸-天門冬氨酸轉運體
外观
兴奋性氨基酸转运蛋白 1 ( EAAT1 )是一种蛋白质,在人类中由SLC1A3基因编码。 [7] EAAT1 也常被称为谷氨酸天冬氨酸转运蛋白 1 ( GLAST-1 )。
EAAT1 主要在质膜中表达,使其能够从细胞外空间去除谷氨酸。 [8]它还位于线粒体内膜,并参与到苹果酸穿梭的过程当中。 [9]
机制
[编辑]EAAT1在体内以同型三聚体的形式发挥作用。 [10] EAAT1 介导谷氨酸和天冬氨酸的运输,其中包括三个Na +和一个H +阳离子的同向运输以及一个K +阳离子的反向运输。这种共转运偶联作用(或同向转运)允许谷氨酸逆着浓度梯度转运到细胞内。 [11]
组织分布
[编辑]EAAT1 在整个中枢神经系统都有表达, [12]并且在小脑的星形胶质细胞和伯格曼胶质细胞中高度表达。 [13] [14]在视网膜中,EAAT1 在穆勒细胞中表达。 [15] EAAT1 也在许多其他组织中表达,包括心肌细胞。 [9]
临床意义
[编辑]它与 6 型发作性共济失调有关。 [16] EAAT1表达也可能与骨关节炎有关。 [17]
药理
[编辑]DL-苏式-β-苄氧天冬氨酸 (TBOA) 是一种兴奋性氨基酸转运蛋白的抑制剂。 [18]
参考
[编辑]- ^ 與L-穀氨酸-天門冬氨酸轉運體相關的疾病;在維基數據上查看/編輯參考.
- ^ 對solute carrier family 1 member 3起作用的藥物;在維基數據上查看/編輯參考.
- ^ 3.0 3.1 3.2 GRCh38: Ensembl release 89: ENSG00000079215 - Ensembl, May 2017
- ^ 4.0 4.1 4.2 GRCm38: Ensembl release 89: ENSMUSG00000005360 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3. [2024-04-22]. (原始内容存档于2009-05-09).
- ^ Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC. Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. The Journal of Neuroscience. March 1995, 15 (3 Pt 1): 1835–53. PMC 6578153 . PMID 7891138. doi:10.1523/JNEUROSCI.15-03-01835.1995.
- ^ 9.0 9.1 Ralphe JC, Segar JL, Schutte BC, Scholz TD. Localization and function of the brain excitatory amino acid transporter type 1 in cardiac mitochondria. Journal of Molecular and Cellular Cardiology. July 2004, 37 (1): 33–41. PMID 15242733. doi:10.1016/j.yjmcc.2004.04.008.
- ^ Gendreau S, Voswinkel S, Torres-Salazar D, Lang N, Heidtmann H, Detro-Dassen S, Schmalzing G, Hidalgo P, Fahlke C. A trimeric quaternary structure is conserved in bacterial and human glutamate transporters. The Journal of Biological Chemistry. September 2004, 279 (38): 39505–12. PMID 15265858. S2CID 16077315. doi:10.1074/jbc.M408038200 .
- ^ Kanai Y, Hediger MA. The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflügers Archiv. February 2004, 447 (5): 469–79. PMID 14530974. S2CID 21564906. doi:10.1007/s00424-003-1146-4.
- ^ Danbolt NC. Glutamate uptake. Progress in Neurobiology. September 2001, 65 (1): 1–105. PMID 11369436. S2CID 27347413. doi:10.1016/S0301-0082(00)00067-8.
- ^ Storck T, Schulte S, Hofmann K, Stoffel W. Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. Proceedings of the National Academy of Sciences of the United States of America. November 1992, 89 (22): 10955–9. Bibcode:1992PNAS...8910955S. PMC 50461 . PMID 1279699. doi:10.1073/pnas.89.22.10955 .
- ^ Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW. Localization of neuronal and glial glutamate transporters. Neuron. September 1994, 13 (3): 713–25. PMID 7917301. S2CID 45299639. doi:10.1016/0896-6273(94)90038-8 .
- ^ Rauen T, Taylor WR, Kuhlbrodt K, Wiessner M. High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance. Cell and Tissue Research. January 1998, 291 (1): 19–31. PMID 9394040. S2CID 6814592. doi:10.1007/s004410050976.
- ^ Jen JC, Wan J, Palos TP, Howard BD, Baloh RW. Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures. Neurology. August 2005, 65 (4): 529–34. PMID 16116111. S2CID 22492395. doi:10.1212/01.WNL.0000172638.58172.5a.
- ^ Mason DJ, Brakspear K, Wilson C, Williams R, Kotwal RS. Expression of glutamate receptors and transporters in human subchondral bone in osteoarthritis. Orthopaedic Proceedings (The British Editorial Society of Bone & Joint Surgery). July 2010, 93–B (SUPP_I): 411 [2024-04-22]. doi:10.1302/0301-620X.93BSUPP_I.0930069b (不活跃 31 January 2024). (原始内容存档于2019-05-08).
- ^ Shimamoto K, Lebrun B, Yasuda-Kamatani Y, Sakaitani M, Shigeri Y, Yumoto N, Nakajima T. DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Molecular Pharmacology. February 1998, 53 (2): 195–201. PMID 9463476. doi:10.1124/mol.53.2.195.