Characterization of the role of TMEM175 in an in vitro lysosomal H+ fluxes model
文献类型：期刊论文
| 作者 | Yang, Chuanyan2,3; Tian, Fuyun2,4; Hu, Mei2,5; Kang, Chunlan2,6; Ping, Meixuan2,4,7; Liu, Yiyao2; Hu, Meiqin9; Xu, Haoxing9; Yu, Ye3,8; Gao, Zhaobing1,2,4,7
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| 刊名 | FEBS JOURNAL
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| 出版日期 | 2023-05-19 |
| 页码 | 19 |
| 关键词 | glycocalyx H+ leak lysosome acidification proton channel TMEM175 |
| ISSN号 | 1742-464X |
| DOI | 10.1111/febs.16814 |
| 通讯作者 | Yu, Ye(yuye@cpu.edu.cn) ; Gao, Zhaobing(zbgao@simm.ac.cn) ; Li, Ping(lipingt@simm.ac.cn) |
| 英文摘要 | Lysosome acidification is a dynamic equilibrium of H+ influx and efflux across the membrane, which is crucial for cell physiology. The vacuolar H+ ATPase (V-ATPase) is responsible for the H+ influx or refilling of lysosomes. TMEM175 was identified as a novel H+ permeable channel on lysosomal membranes, and it plays a critical role in lysosome acidification. However, how TMEM175 participates in lysosomal acidification remains unknown. Here, we present evidence that TMEM175 regulates lysosomal H+ influx and efflux in enlarged lysosomes isolated from COS1 treated with vacuolin-1. By utilizing the whole-endolysosome patch-clamp recording technique, a series of integrated lysosomal H+ influx and efflux signals in a ten-of-second time scale under the physiological pH gradient (luminal pH 4.60, and cytosolic pH 7.20) was recorded from this in vitro system. Lysosomal H+ fluxes constitute both the lysosomal H+ refilling and releasing, and they are asymmetrical processes with distinct featured kinetics for each of the H+ fluxes. Lysosomal H+ fluxes are entirely abolished when TMEM175 losses of function in the F39V mutant and is blocked by the antagonist (2-GBI). Meanwhile, lysosomal H+ fluxes are modulated by the pH-buffering capacity of the lumen and the lysosomal glycosylated membrane proteins, lysosome-associated membrane protein 1 (LAMP1). We propose that the TMEM175-mediated lysosomal H+ fluxes model would provide novel thoughts for studying the pathology of Parkinson's disease and lysosome storage disorders. |
| WOS关键词 | PROTON CHANNEL ; ION CHANNELS ; MEMBRANE ; ACIDIFICATION ; INHIBITION ; PERMEATION ; MECHANISM ; PROTEINS ; VESICLES ; CHLORIDE |
| 资助项目 | National Natural Science Foundation of China[32100621] ; National Natural Science Foundation of China[82273913] ; Guangdong Basic and Applied Basic Research Foundation[2022A1515010851] ; Zhongshan Municipal Bureau of Science and Technology[220418134367984] ; Zhongshan Municipal Bureau of Science and Technology[210724194041939] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022013] ; Department of Science and Technology of Guangdong Province[2019B090904008] ; Department of Science and Technology of Guangdong Province ; High-level new RD institute ; [2021B0909050003] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000991480600001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306599]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Yu, Ye; Gao, Zhaobing; Li, Ping |
| 作者单位 | 1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Beijing, Peoples R China 3.China Pharmaceut Univ, Dept Basic Med & Clin Pharm, Nanjing, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Beijing, Peoples R China 5.Guangzhou Univ Chinese Med, Zhongshan Hosp, Pharmacol Lab, Guangzhou, Peoples R China 6.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Peoples R China 7.Univ Chinese Acad Sci, Beijing, Peoples R China 8.China Pharmaceut Univ, Dept Basic Med & Clin Pharm, Nanjing 210009, Peoples R China 9.Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI USA |
| 推荐引用方式 GB/T 7714 | Yang, Chuanyan,Tian, Fuyun,Hu, Mei,et al. Characterization of the role of TMEM175 in an in vitro lysosomal H+ fluxes model[J]. FEBS JOURNAL,2023:19. |
| APA | Yang, Chuanyan.,Tian, Fuyun.,Hu, Mei.,Kang, Chunlan.,Ping, Meixuan.,...&Li, Ping.(2023).Characterization of the role of TMEM175 in an in vitro lysosomal H+ fluxes model.FEBS JOURNAL,19. |
| MLA | Yang, Chuanyan,et al."Characterization of the role of TMEM175 in an in vitro lysosomal H+ fluxes model".FEBS JOURNAL (2023):19. |
入库方式： OAI收割
来源：上海药物研究所
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