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 |