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DOI | 10.1073/pnas.1922714117 |
A paradigm of thermal adaptation in penguins and elephants by tuning cold activation in TRPM8 | |
Yang S.; Lu X.; Wang Y.; Xu L.; Chen X.; Yang F.; Lai R. | |
发表日期 | 2020 |
ISSN | 0027-8424 |
起始页码 | 8633 |
结束页码 | 8638 |
卷号 | 117期号:15 |
英文摘要 | To adapt to habitat temperature, vertebrates have developed sophisticated physiological and ecological mechanisms through evolution. Transient receptor potential melastatin 8 (TRPM8) serves as the primary sensor for cold. However, how cold activates TRPM8 and how this sensor is tuned for thermal adaptation remain largely unknown. Here we established a molecular framework of how cold is sensed in TRPM8 with a combination of patch-clamp recording, unnatural amino acid imaging, and structural modeling. We first observed that the maximum cold activation of TRPM8 in eight different vertebrates (i.e., African elephant and emperor penguin) with distinct side-chain hydrophobicity (SCH) in the pore domain (PD) is tuned to match their habitat temperature. We further showed that altering SCH for residues in the PD with solvent-accessibility changes leads to specific tuning of the cold response in TRPM8. We also observed that knockin mice expressing the penguin's TRPM8 exhibited remarkable tolerance to cold. Together, our findings suggest a paradigm of thermal adaptation in vertebrates, where the evolutionary tuning of the cold activation in the TRPM8 ion channel through altering SCH and solvent accessibility in its PD largely contributes to the setting of the cold-sensitive/ tolerant phenotype. © 2020 National Academy of Sciences. All rights reserved. |
英文关键词 | Cold activation; Pore domain; Side-chain hydrophobicity; Thermal adaptation; TRPM8 |
语种 | 英语 |
scopus关键词 | transient receptor potential channel M8; transient receptor potential channel M; animal experiment; Article; cold acclimatization; cold tolerance; conformational transition; elephant; environmental temperature; hydrophobicity; molecular evolution; molecular imaging; nonhuman; patch clamp technique; penguin; priority journal; protein analysis; protein function; structural model; thermodynamics; adaptation; amino acid sequence; animal; channel gating; cold; elephant; genetics; metabolism; penguin; physiology; sequence homology; Adaptation, Physiological; Amino Acid Sequence; Animals; Cold Temperature; Elephants; Ion Channel Gating; Sequence Homology; Spheniscidae; TRPM Cation Channels |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/160994 |
作者单位 | Yang, S., Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China, College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, China; Lu, X., Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China, College of Life Sciences, University of Chinese Academy of Sciences, Bejing, 100049, China; Wang, Y., Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China, College of Wildlife and Protected Area, Northeast Forestry University, Harbin, 150040, Ch... |
推荐引用方式 GB/T 7714 | Yang S.,Lu X.,Wang Y.,et al. A paradigm of thermal adaptation in penguins and elephants by tuning cold activation in TRPM8[J],2020,117(15). |
APA | Yang S..,Lu X..,Wang Y..,Xu L..,Chen X..,...&Lai R..(2020).A paradigm of thermal adaptation in penguins and elephants by tuning cold activation in TRPM8.Proceedings of the National Academy of Sciences of the United States of America,117(15). |
MLA | Yang S.,et al."A paradigm of thermal adaptation in penguins and elephants by tuning cold activation in TRPM8".Proceedings of the National Academy of Sciences of the United States of America 117.15(2020). |
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