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Bestrophin-2和谷氨酰胺合成酶形成一个复合体来进行谷氨酸释放
作者:小柯机器人 发布时间:2022/10/29 14:12:12

美国哥伦比亚大学杨婷婷等研究人员合作发现,Bestrophin-2和谷氨酰胺合成酶形成一个复合体来进行谷氨酸释放。2022年10月26日,《自然》杂志在线发表了这项成果。

研究人员发现了Bestrophin-2(BEST2)对谷氨酸的定向渗透性,严重偏向于谷氨酸输出,确定谷氨酰胺合成酶(GS)是BEST2在眼睛睫状体的结合伙伴,并解析了BEST2-GS复合物的结构。BEST2通过将GS拴在细胞膜上降低了细胞膜的活性。GS通过BEST2的中心腔延伸BEST2的离子传导通路,在没有细胞内谷氨酸的情况下抑制BEST2通道功能,但使BEST2对细胞内谷氨酸敏感,促进BEST2的开放,从而解除GS的抑制作用。研究人员证明了BEST2在传导氯化物和谷氨酸方面的生理作用以及GS在非色素性睫状上皮细胞中的影响。

总之,这些结果揭示了通过BEST2-GS释放谷氨酸的新机制。

据了解,BEST2是bestrophin家族中的一个钙激活阴离子通道的成员,在眼部生理学中具有关键作用。

附:英文原文

Title: Bestrophin-2 and glutamine synthetase form a complex for glutamate release

Author: Owji, Aaron P., Yu, Kuai, Kittredge, Alec, Wang, Jiali, Zhang, Yu, Yang, Tingting

Issue&Volume: 2022-10-26

Abstract: Bestrophin-2 (BEST2) is a member of the bestrophin family of calcium-activated anion channels that has a critical role in ocular physiology1,2,3,4. Here we uncover a directional permeability of BEST2 to glutamate that heavily favours glutamate exit, identify glutamine synthetase (GS) as a binding partner of BEST2 in the ciliary body of the eye, and solve the structure of the BEST2–GS complex. BEST2 reduces cytosolic GS activity by tethering GS to the cell membrane. GS extends the ion conducting pathway of BEST2 through its central cavity and inhibits BEST2 channel function in the absence of intracellular glutamate, but sensitizes BEST2 to intracellular glutamate, which promotes the opening of BEST2 and thus relieves the inhibitory effect of GS. We demonstrate the physiological role of BEST2 in conducting chloride and glutamate and the influence of GS in non-pigmented ciliary epithelial cells. Together, our results reveal a novel mechanism of glutamate release through BEST2–GS.

DOI: 10.1038/s41586-022-05373-x

Source: https://www.nature.com/articles/s41586-022-05373-x

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html