L-穀氨酸-天門冬氨酸轉運體

興奮性氨基酸轉運蛋白 1 （ EAAT1 ）是一種蛋白質，在人類中由SLC1A3基因編碼。 ^[7] EAAT1 也常被稱為穀氨酸天冬氨酸轉運蛋白 1 ( GLAST-1 )。

L-穀氨酸-天門冬氨酸轉運體
識別號
別名	SLC1A3；, EA6, EAAT1, GLAST, GLAST1, solute carrier family 1 member 3
外部ID	OMIM：600111 MGI：99917 HomoloGene：20882 GeneCards：SLC1A3
相關疾病
episodic ataxia type 6[1]
為以下藥物的標靶
DL-TBOA[2]
基因位置（人類） 染色體 5號染色體[3] 基因座 5p13.2 起始 36,596,588 bp[3] 終止 36,688,334 bp[3]
基因位置（小鼠） 染色體 小鼠15號染色體[4] 基因座 15 A1|15 3.82 cM 起始 8,663,608 bp[4] 終止 8,740,248 bp[4]
RNA表達模式
查閱更多表達數據
基因本體 分子功能 • amino acid binding • symporter activity • glutamate binding • L-glutamate transmembrane transporter activity • amino acid transmembrane transporter activity • high-affinity glutamate transmembrane transporter activity • acidic amino acid transmembrane transporter activity • glutamate:sodium symporter activity • 金屬離子結合 細胞組分 • integral component of membrane • cell projection • 膜 • 細胞膜 • cell surface • neuronal cell body • neuron projection • cell periphery • integral component of plasma membrane 生物學過程 • 化學性突觸傳遞 • gamma-aminobutyric acid biosynthetic process • glutamate biosynthetic process • neuromuscular process controlling balance • response to light stimulus • cell morphogenesis involved in neuron differentiation • cranial nerve development • response to antibiotic • ion transport • 聽覺 • glutamate secretion • auditory behavior • neurotransmitter uptake • response to wounding • positive regulation of synaptic transmission • glutamate metabolic process • L-glutamate import • amino acid transport • D-aspartate import across plasma membrane • potassium ion transmembrane transport • L-glutamate import across plasma membrane • L-aspartate import across plasma membrane • chloride transmembrane transport • L-glutamate transmembrane transport Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	6507	20512
Ensembl	ENSG00000079215	ENSMUSG00000005360
UniProt	P43003	P56564
mRNA​序列	NM_001166695 ​NM_001166696 ​NM_001289939 ​NM_001289940 ​NM_004172	NM_148938
蛋白序列	NP_001160167 ​NP_001160168 ​NP_001276868 ​NP_001276869 ​NP_004163	NP_683740
基因位置​（UCSC）	Chr 5: 36.6 – 36.69 Mb	Chr 15: 8.66 – 8.74 Mb
PubMed​查找	[5]	[6]
維基數據
檢視/編輯人類 檢視/編輯小鼠

EAAT1 主要在質膜中表達，使其能夠從細胞外空間去除穀氨酸。 ^[8]它還位於線粒體內膜，並參與到蘋果酸穿梭的過程當中。 ^[9]

機制

EAAT1在體內以同型三聚體的形式發揮作用。 ^[10] EAAT1 介導穀氨酸和天冬氨酸的運輸，其中包括三個Na ⁺和一個H ⁺陽離子的同向運輸以及一個K ⁺陽離子的反向運輸。這種共轉運偶聯作用（或同向轉運）允許穀氨酸逆着濃度梯度轉運到細胞內。 ^[11]

• 
  蘋果酸-天冬氨酸穿梭的圖解
• 
  SLC1A3 在伯格曼神經膠質纖維中的表達。 出生後第7天小鼠大腦矢狀切面；GENSAT數據庫。

組織分佈

EAAT1 在整個中樞神經系統都有表達， ^[12]並且在小腦的星形膠質細胞和伯格曼膠質細胞中高度表達。 ^{[13] [14]}在視網膜中，EAAT1 在穆勒細胞中表達。 ^[15] EAAT1 也在許多其他組織中表達，包括心肌細胞。 ^[9]

臨床意義

它與 6 型發作性共濟失調有關。 ^[16] EAAT1表達也可能與骨關節炎有關。 ^[17]

藥理

DL-蘇式-β-苄氧天冬氨酸 (TBOA) 是一種興奮性氨基酸轉運蛋白的抑制劑。 ^[18]

參考

1. 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.
2. 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. GRCh38: Ensembl release 89: ENSG00000079215 - Ensembl, May 2017
4. GRCm38: Ensembl release 89: ENSMUSG00000005360 - Ensembl, May 2017
5. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
6. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
7. Entrez Gene: SLC1A3 solute carrier family 1 (glial high affinity glutamate transporter), member 3. [2024-04-22]. （原始內容存檔於2009-05-09）.
8. 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. 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.
10. 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 .
11. 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.
12. 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.
13. 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 .
14. 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 .
15. 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.
16. 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.
17. 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 (不活躍 31 January 2024). （原始內容存檔於2019-05-08）.
18. 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.