Molecular mechanisms of STIM/Orai communication

Ca(2+)entry into the cell via store-operated Ca(2+)release-activated Ca(2+)(CRAC) channels triggers diverse signaling cascades that affect cellular processes like cell growth, gene regulation, secretion, and cell death. These store-operated Ca(2+)channels open after depletion of intracellular Ca(2+)...

Full description

Saved in:
Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2016-04, Vol.310 (8), p.C643-C662
Main Authors: Derler, Isabella, Jardin, Isaac, Romanin, Christoph
Format: Article
Language:English
Subjects:
Binding Sites
Calcium
Calcium - chemistry
Calcium - metabolism
Calcium Signaling
Genes
Humans
Ion Channel Gating
Ion Transport
Ions
Membrane Proteins
Models, Biological
Models, Chemical
Models, Molecular
Molecules
Mutagenesis
Neoplasm Proteins - chemistry
Neoplasm Proteins - metabolism
Neoplasm Proteins - ultrastructure
ORAI1 Protein - chemistry
ORAI1 Protein - metabolism
ORAI1 Protein - ultrastructure
Protein Binding
Protein Conformation
Proteins
Stromal Interaction Molecule 1 - chemistry
Stromal Interaction Molecule 1 - metabolism
Stromal Interaction Molecule 1 - ultrastructure
Themes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ca(2+)entry into the cell via store-operated Ca(2+)release-activated Ca(2+)(CRAC) channels triggers diverse signaling cascades that affect cellular processes like cell growth, gene regulation, secretion, and cell death. These store-operated Ca(2+)channels open after depletion of intracellular Ca(2+)stores, and their main features are fully reconstituted by the two molecular key players: the stromal interaction molecule (STIM) and Orai. STIM represents an endoplasmic reticulum-located Ca(2+)sensor, while Orai forms a highly Ca(2+)-selective ion channel in the plasma membrane. Functional as well as mutagenesis studies together with structural insights about STIM and Orai proteins provide a molecular picture of the interplay of these two key players in the CRAC signaling cascade. This review focuses on the main experimental advances in the understanding of the STIM1-Orai choreography, thereby establishing a portrait of key mechanistic steps in the CRAC channel signaling cascade. The focus is on the activation of the STIM proteins, the subsequent coupling of STIM1 to Orai1, and the consequent structural rearrangements that gate the Orai channels into the open state to allow Ca(2+)permeation into the cell.
ISSN:0363-6143
1522-1563
1522-1563
DOI:10.1152/ajpcell.00007.2016