Title E-syt1 Re-arranges STIM1 Clusters to Stabilize Ring-shaped ER-PM Contact Sites and Accelerate Ca2+ Store Replenishment
Authors Kang, Fei
Zhou, Mengxuan
Huang, Xiaoshuai
Fang, Junchao
Wei, Lisi
Boulanger, Jerome
Liu, Zengzhen
Salamero, Jean
Liu, Yanmei
Chen, Liangyi
Affiliation Peking Univ, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, State Key Lab Membrane Biol, Beijing 100871, Peoples R China
Huazhong Univ Sci & Technol, Minist Educ China, Sch Automat, Key Lab Image Proc & Intelligent Control, Wuhan 430074, Hubei, Peoples R China
PSL Res Univ, CNRS, Inst Curie, UMR 144, Paris, France
PSL Res Univ, Inst Curie, Cell & Tissue Imaging Facil, Paris, France
Issue Date 2019
Publisher SCIENTIFIC REPORTS
Abstract In many non-excitable cells, the depletion of endoplasmic reticulum (ER) Ca2+ stores leads to the dynamic formation of membrane contact sites (MCSs) between the ER and the plasma membrane (PM), which activates the store-operated Ca2+ entry (SOCE) to refill the ER store. Two different Ca(2+)sensitive proteins, STIM1 and extended synaptotagmin-1 (E-syt1), are activated during this process. Due to the lack of live cell super-resolution imaging, how MCSs are dynamically regulated by STIM1 and E-syt1 coordinately during ER Ca2+ store depletion and replenishment remain unknown. With homebuilt super-resolution microscopes that provide superior axial and lateral resolution in live cells, we revealed that extracellular Ca2+ influx via SOCE activated E-syt1s to move towards the PM by similar to 12 nm. Unexpectedly, activated E-syt1s did not constitute the MCSs per se, but re-arranged neighboring ER structures into ring-shaped MCSs (230 similar to 280 nm in diameter) enclosing E-syt1 puncta, which helped to stabilize MCSs and accelerate local ER Ca2+ replenishment. Overall, we have demonstrated different roles of STIM1 and E-syt1 in MCS formation regulation, SOCE activation and ER Ca2+ store replenishment.
URI http://hdl.handle.net/20.500.11897/549996
ISSN 2045-2322
DOI 10.1038/s41598-019-40331-0
Indexed SCI(E)
EI
Appears in Collections: 分子医学研究所
膜生物学国家重点实验室

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