Evidence map›Paper›PMID 41238795›Full record

ArticleEMBO reports2025

Rational tuning of temperature sensitivity of the TRPM8 channel.

Lizhen Xu, Xiao Liang, Yunfei Wang, Han Wen, Wenxuan Zhen, Zhangzhi Xue, Fangfei Zhang, Xiao Yi, Xiaoying Chen, Lidan Hu and 8 more

Abstract read
In one paragraph

Article in EMBO reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Deep mutational scan of the pore of the cold-sensing TRPM8 channel.bioRxiv : the preprint server for biology · 2026
    Article
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

18 authors.

Lizhen Xu *Kidney Disease Center of the First Affiliated Hospital and Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.ORCID 0000-0003-4921-7238
Xiao Liang *Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China.ORCID 0000-0002-2476-7332
Yunfei Wang *College of Wildlife and Protected Area, Northeast Forestry University, 150040, Harbin, Heilongjiang Province, China.ORCID 0000-0001-7693-0595
Han Wen *DP Technology, Beijing, China.
Wenxuan ZhenKidney Disease Center of the First Affiliated Hospital and Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Zhangzhi XueWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China.
Fangfei ZhangWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China.
Xiao YiWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China.
Xiaoying ChenKidney Disease Center of the First Affiliated Hospital and Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Lidan HuThe Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, China.
Bei LiAlibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, China.
Bing ZhangAlibaba-Zhejiang University Joint Research Center of Future Digital Healthcare, Hangzhou, China.
Zhenfeng DengDP Technology, Beijing, China.ORCID 0009-0006-3881-9312
Wei YangKidney Disease Center of the First Affiliated Hospital and Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.ORCID 0000-0003-3065-1843
Shilong YangCollege of Wildlife and Protected Area, Northeast Forestry University, 150040, Harbin, Heilongjiang Province, China. syang2020@nefu.edu.cn.ORCID 0000-0002-2618-1837
Tiannan GuoWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China. guotiannan@westlake.edu.cn.ORCID 0000-0003-3869-7651
Yi ZhuWestlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China. zhuyi@westlake.edu.cn.ORCID 0000-0003-0429-0802
Fan YangKidney Disease Center of the First Affiliated Hospital and Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. fanyanga@zju.edu.cn.ORCID 0000-0002-0520-5254

Funding

Hangzhou Agriculture and Society Advancement Program 20190101A04MOST | National Natural Science Foundation of China (NSFC) 32421001,32571328,32122040,31971040 and 31800990MOST | National Natural Science Foundation of China (NSFC) 81972492 and 21904107MOST | NSFC | National Natural Science Foundation of China-Zhejiang Joint Fund for the Integration of Industrialization and Informatization (NSFC-Zhejiang Joint Fund) LR19C050001MOST | NSFC | National Natural Science Foundation of China-Zhejiang Joint Fund for the Integration of Industrialization and Informatization (NSFC-Zhejiang Joint Fund) RG25C050001 and LR20C050002
6 · The paper itself

Abstract

Detecting temperature is crucial for the survival of living organisms. Although the temperature sensitive Transient Receptor Potential Melastatin 8 (TRPM8) channel has been identified as the prototypical cold sensor, the mechanisms by which it detects temperature remain elusive. In this study, we first identify groups of clustered residues that undergo conformational rearrangements between buried and exposed states during cold activation by hydroxyl radical footprinting-mass spectrometry (HRF-MS). By systematically perturbing water-protein interactions at these residues with point mutations that change side chain hydrophobicity (SCH), we achieve rational tuning of temperature sensitivity in this channel. Specifically, mutations with the clearest impacts on TRPM8 cold sensitivity are clustered in the MHR1-3 domains, where the protein of isolated MHR1-3 domains also exhibits clear conformational rearrangements in response to cold. Guided by this mechanism, we rationally edit the Trpm8 gene in mice, introducing a single point mutation to render them insensitive to coldness.

Indexed as

TRPM Cation ChannelsAnimalsCold TemperatureHEK293 CellsHumansHydrophobic and Hydrophilic InteractionsMiceModels, MolecularPoint MutationProtein ConformationProtein DomainsTemperatureThermosensingTRPM8 protein, humanTRPM8 protein, mouseTRPM Cation ChannelsConformational RearrangementsTemperature SensingTRPM8 ChannelWater–Protein Interactions

Identifiers

PMID41238795
PMCPMC12715194

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Registered trials

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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.