Inside-out Ca(2+) signalling prompted by STIM1 conformational switch

Store-operated Ca(2+) entry mediated by STIM1 and ORAI1 constitutes one of the major Ca(2+) entry routes in mammalian cells. The molecular choreography of STIM1-ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca(2+) store depletion with subsequent oligomerization of the STIM1 ER-luminal do...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2015-07, Vol.6, p.7826-7826
Main Authors: Ma, Guolin, Wei, Ming, He, Lian, Liu, Chongxu, Wu, Bo, Zhang, Shenyuan L, Jing, Ji, Liang, Xiaowen, Senes, Alessandro, Tan, Peng, Li, Siwei, Sun, Aomin, Bi, Yunchen, Zhong, Ling, Si, Hongjiang, Shen, Yuequan, Li, Minyong, Lee, Mi-Sun, Zhou, Weibin, Wang, Junfeng, Wang, Youjun, Zhou, Yubin
Format: Article
Language:English
Subjects:
Calcium Channels - metabolism
Calcium Signaling
Chromatography, Liquid
Circular Dichroism
Endoplasmic Reticulum - metabolism
Escherichia coli
Green Fluorescent Proteins
HEK293 Cells
HeLa Cells
Humans
Luminescent Proteins
Membrane Proteins - metabolism
Microscopy, Confocal
Models, Molecular
Native Polyacrylamide Gel Electrophoresis
Neoplasm Proteins - metabolism
Nuclear Magnetic Resonance, Biomolecular
ORAI1 Protein
Patch-Clamp Techniques
Protein Conformation
Recombinant Proteins
Red Fluorescent Protein
Spectrometry, Fluorescence
Stromal Interaction Molecule 1
Surface Plasmon Resonance
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Store-operated Ca(2+) entry mediated by STIM1 and ORAI1 constitutes one of the major Ca(2+) entry routes in mammalian cells. The molecular choreography of STIM1-ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca(2+) 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 Ca(2+) 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.
ISSN:2041-1723
DOI:10.1038/ncomms8826