Dataset Information

Identification of molecular determinants that govern distinct STIM2 activation dynamics.

ABSTRACT: The endoplasmic reticulum (ER) Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2, which connect ER Ca2+ depletion with extracellular Ca2+ influx, are crucial for the maintenance of Ca2+ homeostasis in mammalian cells. Despite the recent progress in unraveling the role of STIM2 in Ca2+ signaling, the mechanistic underpinnings of its activation remain underexplored. We use an engineering approach to direct ER-resident STIMs to the plasma membrane (PM) while maintaining their correct membrane topology, as well as Förster resonance energy transfer (FRET) sensors that enabled in cellulo real-time monitoring of STIM activities. This allowed us to determine the calcium affinities of STIM1 and STIM2 both in cellulo and in situ, explaining the current discrepancies in the literature. We also identified the key structural determinants, especially the corresponding G residue in STIM1, which define the distinct activation dynamics of STIM2. The chimeric E470G mutation could switch STIM2 from a slow and weak Orai channel activator into a fast and potent one like STIM1 and vice versa. The systemic dissection of STIM2 activation by protein engineering sets the stage for the elucidation of the regulation and function of STIM2-mediated signaling in mammals.

SUBMITTER: Zheng S

PROVIDER: S-EPMC6267984 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Identification of molecular determinants that govern distinct STIM2 activation dynamics.

Zheng Sisi S Ma Guolin G He Lian L Zhang Tian T Li Jia J Yuan Xiaoman X Nguyen Nhung T NT Huang Yun Y Zhang Xiaoyan X Gao Ping P Nwokonko Robert R Gill Donald L DL Dong Hao H Zhou Yubin Y Wang Youjun Y

PLoS biology 20181116 11

The endoplasmic reticulum (ER) Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2, which connect ER Ca2+ depletion with extracellular Ca2+ influx, are crucial for the maintenance of Ca2+ homeostasis in mammalian cells. Despite the recent progress in unraveling the role of STIM2 in Ca2+ signaling, the mechanistic underpinnings of its activation remain underexplored. We use an engineering approach to direct ER-resident STIMs to the plasma membrane (PM) while maintaining their correct me ...[more]

PMID: 30444880

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Dataset Information

Identification of molecular determinants that govern distinct STIM2 activation dynamics.

Publications

Identification of molecular determinants that govern distinct STIM2 activation dynamics.

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