Tetrandrine regulates NAADP-mediated calcium signaling through a LIMP-2-dependent and sphingosine-mediated mechanism
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| Publicat a: | Nature Communications vol. 16, no. 1 (2025), p. 6308 |
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| Altres autors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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|---|---|---|---|
| 001 | 3228184762 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2041-1723 | ||
| 024 | 7 | |a 10.1038/s41467-025-61565-9 |2 doi | |
| 035 | |a 3228184762 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 145839 |2 nlm | ||
| 100 | 1 | |a Chan, Wing-Cheung |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 245 | 1 | |a Tetrandrine regulates NAADP-mediated calcium signaling through a LIMP-2-dependent and sphingosine-mediated mechanism | |
| 260 | |b Nature Publishing Group |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Tetrandrine (Tet) is a potent inhibitor of Ebola virus replication by blocking NAADP-dependent calcium release through endolysosomal two-pore channels (TPCs) and a moderately potent anti-tumor agent. Using a clickable photoaffinity probe, we identify lysosomal integral membrane protein-2 (LIMP-2) as a direct target of Tet and a key regulator of this calcium signaling. Tet binds LIMP-2’s ectodomain, inhibiting lysosomal cholesterol and sphingosine transport, which alters lipid metabolism. Tet treatment and LIMP-2 depletion inhibit NAADP-dependent calcium release, reversible by removing lysosomal cholesterol and sphingosine. Sphingosine triggers lysosomal calcium release via TPCs and restores this signaling in Tet-treated or LIMP-2-deficient cells, revealing a LIMP-2-regulated, sphingosine-dependent lysosomal calcium pathway. At higher doses, Tet induces apoptosis through unfolded protein response activation independently of LIMP-2. These findings highlight Tet as a LIMP-2 inhibitor, elucidate its role in calcium signaling and cell death, and suggest therapeutic potential for Tet and LIMP-2 inhibitors in antiviral treatments.Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation. | |
| 653 | |a Endoplasmic reticulum | ||
| 653 | |a Cholesterol | ||
| 653 | |a Calcium signalling | ||
| 653 | |a Lipid metabolism | ||
| 653 | |a Tetrandrine | ||
| 653 | |a Ebola virus | ||
| 653 | |a Labeling | ||
| 653 | |a Chemistry | ||
| 653 | |a Homeostasis | ||
| 653 | |a Mitochondria | ||
| 653 | |a Protein folding | ||
| 653 | |a Viral diseases | ||
| 653 | |a Peptides | ||
| 653 | |a Localization | ||
| 653 | |a Cell culture | ||
| 653 | |a NAADP | ||
| 653 | |a Calcium | ||
| 653 | |a Proteins | ||
| 653 | |a Cell death | ||
| 653 | |a Apoptosis | ||
| 653 | |a Lipids | ||
| 653 | |a Calcium homeostasis | ||
| 653 | |a Ebolavirus | ||
| 653 | |a Environmental | ||
| 700 | 1 | |a Zhao, Qian |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Wong, Koon Ho |u University of Macau, Avenida da Universidade, Taip, Faculty of Health Sciences, Macau SAR, PR China (GRID:grid.437123.0) (ISNI:0000 0004 1794 8068); University of Macau, Avenida da Universidade, Taipa, Institute of Translational Medicine, Macau SAR, PR China (GRID:grid.437123.0) (ISNI:0000 0004 1794 8068); University of Macau, Avenida da Universidade, Taipa, MoE Frontiers Science Center for Precision Oncology, Macau SAR, PR China (GRID:grid.437123.0) (ISNI:0000 0004 1794 8068) | |
| 700 | 1 | |a Tang, Hok-Him |u The Hong Kong Polytechnic University, Department of Food Science and Nutrition, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, Research Centre for Chinese Medicine Innovation, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Mok, Daniel Kam-Wah |u The Hong Kong Polytechnic University, Department of Food Science and Nutrition, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, Research Centre for Chinese Medicine Innovation, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Pardeshi, Lakhansing |u University of Macau, Avenida da Universidade, Taip, Faculty of Health Sciences, Macau SAR, PR China (GRID:grid.437123.0) (ISNI:0000 0004 1794 8068); University of Macau, Avenida da Universidade, Taipa, Genomics and Bioinformatics Core, Macau SAR, PR China (GRID:grid.437123.0) (ISNI:0000 0004 1794 8068) | |
| 700 | 1 | |a Ruan, Ye Chun |u The Hong Kong Polytechnic University, Department of Biomedical Engineering, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Yang, Yang |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Wong, Chi-Ming |u The Hong Kong Polytechnic University, Department of Health Technology and Informatics, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Wong, Clarence T. T. |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Zhao, Yong-Juan |u The Chinese University of Hong Kong, Ciechanover Institute of Precision and Regenerative Medicine, Shenzhen, PR China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482); The Chinese University of Hong Kong, School of Medicine, Shenzhen, PR China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) | |
| 700 | 1 | |a Chan, Ka Ying |u The Hong Kong Polytechnic University, Department of Health Technology and Informatics, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Yin, Zengsheng |u The University of Hong Kong, Department of Chemistry, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757); The University of Hong Kong, Laboratory for Synthetic Chemistry and Chemical Biology Limited, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757) | |
| 700 | 1 | |a Leung, Howard Ho-Wai |u The Chinese University of Hong Kong, Department of Anatomical and Cellular Pathology, Hong Kong, PR China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) | |
| 700 | 1 | |a Ma, Xiyang |u The Hong Kong Polytechnic University, Department of Biomedical Engineering, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Chau, Mary P. |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Leung, Franco King-Chi |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); Hong Kong Science Park, Centre for Eye and Vision Research, Hong Kong, PR China (GRID:grid.16890.36) | |
| 700 | 1 | |a Lui, Ying-Ying |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); Hong Kong Science Park, Centre for Eye and Vision Research, Hong Kong, PR China (GRID:grid.16890.36) | |
| 700 | 1 | |a Au, Shannon Wing-Ngor |u The Chinese University of Hong Kong, School of Life Sciences, Hong Kong, PR China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) | |
| 700 | 1 | |a Sun, Kailei |u The Chinese University of Hong Kong, School of Life Sciences, Hong Kong, PR China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) | |
| 700 | 1 | |a Mok, Chin Yu |u The Chinese University of Hong Kong, School of Life Sciences, Hong Kong, PR China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) | |
| 700 | 1 | |a Wang, Fang |u University of Macau, Avenida da Universidade, Taip, Faculty of Health Sciences, Macau SAR, PR China (GRID:grid.437123.0) (ISNI:0000 0004 1794 8068) | |
| 700 | 1 | |a Ma, Cong |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Ho, Yu-Hin |u The University of Hong Kong, Department of Chemistry, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757); The University of Hong Kong, Laboratory for Synthetic Chemistry and Chemical Biology Limited, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757) | |
| 700 | 1 | |a Ye, Xiang-Yang |u Hangzhou Normal University, School of Pharmacy, Hangzhou, PR China (GRID:grid.410595.c) (ISNI:0000 0001 2230 9154); Hangzhou Normal University, Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou, PR China (GRID:grid.410595.c) (ISNI:0000 0001 2230 9154); Hangzhou Normal University, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou, PR China (GRID:grid.410595.c) (ISNI:0000 0001 2230 9154); Hangzhou Normal University, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou, PR China (GRID:grid.410595.c) (ISNI:0000 0001 2230 9154) | |
| 700 | 1 | |a Yeung, Man Lung |u The University of Hong Kong, Department of Microbiology, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757) | |
| 700 | 1 | |a Zhang, Yajing |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Zhao, Yan Xiang |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Liu, Jiang |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Wong, Ka-Hing |u The Hong Kong Polytechnic University, Department of Food Science and Nutrition, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, Research Institute for Future Food, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Chow, Larry M. C. |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 700 | 1 | |a Li, Xiang David |u The University of Hong Kong, Department of Chemistry, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757); The University of Hong Kong, Laboratory for Synthetic Chemistry and Chemical Biology Limited, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757) | |
| 700 | 1 | |a Tse, Gary M. |u The Chinese University of Hong Kong, Department of Anatomical and Cellular Pathology, Hong Kong, PR China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482) | |
| 700 | 1 | |a Wong, Man-Kin |u The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, Department of Food Science and Nutrition, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); Hong Kong Science Park, Centre for Eye and Vision Research, Hong Kong, PR China (GRID:grid.16890.36) | |
| 700 | 1 | |a Shen, Xiao |u Ltd, Canton Biologics Co., Guangzhou, PR China (GRID:grid.454193.e) (ISNI:0000 0004 1789 3597) | |
| 700 | 1 | |a Chiu, Pauline |u The University of Hong Kong, Department of Chemistry, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757); The University of Hong Kong, Laboratory for Synthetic Chemistry and Chemical Biology Limited, Hong Kong, PR China (GRID:grid.194645.b) (ISNI:0000 0001 2174 2757) | |
| 700 | 1 | |a Ko, Ben C. B. |u The Hong Kong Polytechnic University, Department of Applied Biology and Chemical Technology, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123); The Hong Kong Polytechnic University, State Key Laboratory of Chemical Biology and Drug Discovery, Hong Kong, PR China (GRID:grid.16890.36) (ISNI:0000 0004 1764 6123) | |
| 773 | 0 | |t Nature Communications |g vol. 16, no. 1 (2025), p. 6308 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
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