Volume 29, No 2, Feb 2019
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 29 Issue 2, February 2019: 95-109
ORIGINAL ARTICLES
STIM1 thermosensitivity defines the optimal preference temperature for warm sensation in mice
Xiaoling Liu 1, Haiping Wang 1, Yan Jiang 1, Qin Zheng 2, Matt Petrus 3, Mingmin Zhang 1, Sisi Zheng 4, Christian Schmedt 3, Xinzhong Dong 2 and Bailong Xiao 1
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; 3Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA and 4 Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, 100875 Beijing, China
These authors contributed equally: Xiaoling Liu, Haiping Wang, Yan Jiang, Qin Zheng
Correspondence: Correspondence: Bailong Xiao (xbailong@mail.tsinghua.edu.cn)
Mammals possess a remarkable ability to sense subtle temperature deviations from the thermoneutral skin temperature of ~33 °C, 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 Ca2+ depletion and heat, mediates temperature-induced Ca2+ influx in skin keratinocytes via coupling to Orai Ca2+ channels in plasma membrane. Behaviorally, the keratinocyte-specific knockout of STIM1 shifts the optimal preference temperature (OPT) of mice from ~32 °C to ~34 °C, resulting in a strikingly reversed preference between 32 °C and 34 °C. Importantly, the thermally inactive STIM1-ΔK 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.
https://doi.org/10.1038/s41422-018-0129-0
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