STIM1 thermosensitivity defines the optimal preference temperature for warm sensation in mice  

作　　者：Xiaoling Liu Haiping Wang Yan Jiang Qin Zheng Matt Petrus Mingmin Zhang Sisi Zheng Christian Schmedt Xinzhong Dong Bailong Xiao 

机构地区：[1]State Key Laboratory of Membrane Biology,Tsinghua-Peking Joint Center for Life Sciences,IDG/McGovern Institute for Brain Research,School of Pharmaceutical Sciences, Tsinghua University,100084 Beijing,China [2]Departments of Neuroscience,Neurosurgery,and Dermatology,Center of Sensory Biology,Howard Hughes Medical Institute,the Johns Hopkins University School of Medicine,Baltimore,MD 21205,USA [3]Genomics Institute of the Novartis Research Foundation,San Diego,CA 92121,USA [4]Beijing Key Laboratory of Gene Resource and Molecular Development,College of Life Sciences,Beijing Normal University,100875 Beijing,China

出　　处：《Cell Research》2019年第2期95-109,共15页细胞研究（英文版）

基　　金：the National Natural Science Foundation of China (31371118,31825014,31630090 and 31422027);the National Key R&D Program of China (2016YFA0500402 and 2015CB910102);the Young Thousand Talent Program to B.X.

摘　　要：Mammals possess a remarkable ability to sense subtle temperature deviations from the thermoneutral skin temperature of -33 ℃, which ensures precise warm sensation.However,the underlying mechanisms remain unclear.Here we show that STIM1,an endoplasmic reticulum (ER)resident transmembrane protein that responds to both ER Ca^2- depletion and heat,mediates temperature-induced Ca^2+ influx in skin keratinocytes via coupling to Orai Ca^2+ channels in plasma membrane.Behaviorally,the keratinocyte-specific knockout of STIM1 shifts the optimal preference temperature (OPT)of mice from -32 ℃ to -34℃,resulting in a strikingly reversed preference between 32℃ and 34℃.Importantly,the thermally inactive STIM1-△K knock-in mice show altered OPT and warm preference behaviors as well,demonstrating the requirement of STIM1 thermosensitivity for warm sensation. Furthermore,the wild-type and mutant mice prefer temperatures closer to their respective OPTs,but poorly distinguish temperatures that are equally but oppositely deviated from their OPTs.Mechanistically,keratinocyte STIM1 affects the in vivo warm responses of sensory neurons by likely involving TRPA1 as a downstream transduction channel.Collectively,our data suggest that STIM1 serves as a novel in vivo thermosensor in keratinocytes to define the OPT,which might be utilized as a peripheral reference temperature for precise warm sensation.

关 键 词：STIM1 THERMOSENSITIVITY OPTIMAL preference temperature WARM SENSATION in MICE 

分 类 号：Q[生物学]