Evidence map›Paper›PMID 40628771›Full record

ArticleNature communications2025

Tetrandrine regulates NAADP-mediated calcium signaling through a LIMP-2-dependent and sphingosine-mediated mechanism.

Wing-Cheung Chan, Qian Zhao, Koon Ho Wong, Hok-Him Tang, Daniel Kam-Wah Mok, Lakhansing Pardeshi, Ye Chun Ruan, Yang Yang, Chi-Ming Wong, Clarence T T Wong and 27 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Endosomal TPC1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Virus infection and vesicle trafficking.Frontiers in immunology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

37 authors.

Wing-Cheung ChanDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0003-1558-3192
Qian ZhaoDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0003-2244-6516
Koon Ho WongFaculty of Health Sciences, University of Macau, Avenida da Universidade, Taip, Macau SAR, PR China.ORCID http://orcid.org/0000-0002-9264-5118
Hok-Him TangDepartment of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-8867-9155
Daniel Kam-Wah MokDepartment of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, PR China.
Lakhansing PardeshiFaculty of Health Sciences, University of Macau, Avenida da Universidade, Taip, Macau SAR, PR China.ORCID http://orcid.org/0000-0003-0702-5465
Ye Chun RuanDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-4266-6789
Yang YangDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-1269-2804
Chi-Ming WongDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-0025-7135
Clarence T T WongDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.
Yong-Juan ZhaoCiechanover Institute of Precision and Regenerative Medicine, The Chinese University of Hong Kong, Shenzhen, PR China.ORCID http://orcid.org/0000-0003-4564-1912
Ka Ying ChanDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-7273-4148
Zengsheng YinDepartment of Chemistry, The University of Hong Kong, Hong Kong, PR China.
Howard Ho-Wai LeungDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, PR China.
Xiyang MaDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0003-4983-0315
Mary P ChauDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-7005-9556
Franco King-Chi LeungDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0003-0895-9307
Ying-Ying LuiDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.
Shannon Wing-Ngor AuSchool of Life Sciences, The Chinese University of Hong Kong, Hong Kong, PR China.
Kailei SunSchool of Life Sciences, The Chinese University of Hong Kong, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-5091-4121
Chin Yu MokSchool of Life Sciences, The Chinese University of Hong Kong, Hong Kong, PR China.ORCID http://orcid.org/0009-0001-9314-9431
Fang WangFaculty of Health Sciences, University of Macau, Avenida da Universidade, Taip, Macau SAR, PR China.ORCID http://orcid.org/0000-0002-8965-1015
Cong MaDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0001-9245-0356
Yu-Hin HoDepartment of Chemistry, The University of Hong Kong, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-5941-852X
Xiang-Yang YeSchool of Pharmacy, Hangzhou Normal University, Hangzhou, PR China.ORCID http://orcid.org/0000-0003-3739-0930
Man Lung YeungDepartment of Microbiology, The University of Hong Kong, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-6117-7884
Yajing ZhangDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0001-9930-567X
Yan Xiang ZhaoDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-9408-9979
Jiang LiuDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.
Ka-Hing WongDepartment of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, PR China.
Larry M C ChowDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.
Xiang David LiDepartment of Chemistry, The University of Hong Kong, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-2797-4134
Gary M TseDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, PR China.ORCID http://orcid.org/0000-0002-9405-9665
Man-Kin WongState Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hong Kong, PR China.
Xiao ShenCanton Biologics Co., Ltd, Guangzhou, PR China.ORCID http://orcid.org/0009-0008-3598-1810
Pauline ChiuDepartment of Chemistry, The University of Hong Kong, Hong Kong, PR China. pchiu@hku.hk.
Ben C B KoDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China. ben.ko@polyu.edu.hk.ORCID http://orcid.org/0000-0003-2027-5899

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

BenzylisoquinolinesCalcium SignalingLysosomal Membrane ProteinsNADPSphingosineAnimalsApoptosisCalciumCalcium ChannelsCholesterolHEK293 CellsHumansLysosomesUnfolded Protein ResponseBenzylisoquinolinesCalciumCalcium ChannelsCholesterolLysosomal Membrane ProteinsNAADPNADPSphingosinetetrandrine

Identifiers

PMID40628771
PMCPMC12238253

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.