Inside-out Ca2+ signalling prompted by STIM1 conformational switch

Guolin Ma, Ming Wei, Lian He, Chongxu Liu, Bo Wu, Shenyuan L. Zhang, Ji Jing, Xiaowen Liang, Alessandro Senes, Peng Tan, Siwei Li, Aomin Sun, Yunchen Bi, Ling Zhong, Hongjiang Si, Yuequan Shen, Minyong Li, Mi-Sun Lee, Weibin Zhou, Junfeng Wang (), Youjun Wang () and Yubin Zhou ()
Additional contact information
Guolin Ma: Institute of Biosciences and Technology, Texas A&M University Health Science Center
Ming Wei: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University
Lian He: Institute of Biosciences and Technology, Texas A&M University Health Science Center
Chongxu Liu: High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Bo Wu: High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Shenyuan L. Zhang: College of Medicine, Texas A&M University Health Science Center
Ji Jing: Institute of Biosciences and Technology, Texas A&M University Health Science Center
Xiaowen Liang: Institute of Biosciences and Technology, Texas A&M University Health Science Center
Alessandro Senes: University of Wisconsin Madison
Peng Tan: Institute of Biosciences and Technology, Texas A&M University Health Science Center
Siwei Li: College of Life Sciences, Nankai University
Aomin Sun: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University
Yunchen Bi: High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Ling Zhong: Institute of Biosciences and Technology, Texas A&M University Health Science Center
Hongjiang Si: College of Medicine, Texas A&M University Health Science Center
Yuequan Shen: College of Life Sciences, Nankai University
Minyong Li: Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University
Mi-Sun Lee: University of Michigan Medical School
Weibin Zhou: University of Michigan Medical School
Junfeng Wang: High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences
Youjun Wang: Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University
Yubin Zhou: Institute of Biosciences and Technology, Texas A&M University Health Science Center

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract Store-operated Ca2+ entry mediated by STIM1 and ORAI1 constitutes one of the major Ca2+ entry routes in mammalian cells. The molecular choreography of STIM1–ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca2+ store depletion with subsequent oligomerization of the STIM1 ER-luminal domain, followed by its redistribution towards the plasma membrane to gate ORAI1 channels. The mechanistic underpinnings of this inside-out Ca2+ signalling were largely undefined. By taking advantage of a unique gain-of-function mutation within the STIM1 transmembrane domain (STIM1-TM), here we show that local rearrangement, rather than alteration in the oligomeric state of STIM1-TM, prompts conformational changes in the cytosolic juxtamembrane coiled-coil region. Importantly, we further identify critical residues within the cytoplasmic domain of STIM1 (STIM1-CT) that entail autoinhibition. On the basis of these findings, we propose a model in which STIM1-TM reorganization switches STIM1-CT into an extended conformation, thereby projecting the ORAI-activating domain to gate ORAI1 channels.

Date: 2015
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DOI: 10.1038/ncomms8826

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