title: Structure, regulation and biophysics of I(CRAC), STIM/Orai1.
abstract: Ca(2+) release activated Ca(2+) (CRAC) channels mediate robust Ca(2+) influx when the endoplasmic reticulum Ca(2+) stores are depleted. This essential process for T-cell activation as well as degranulation of mast cells involves the Ca(2+) sensor STIM1, located in the endoplasmic reticulum and the Ca(2+) selective Orai1 channel in the plasma membrane. Our review describes the CRAC signaling pathway, the activation of which is initiated by a drop in the endoplasmic Ca(2+) level sensed by STIM1. This in term induces multimerisation and puncta-formation of STIM1 proteins is followed by their coupling to and activation of Orai channels. Consequently Ca(2+) entry is triggered through the Orai pore into the cytosol with subsequent closure of the channel by Ca(2+)-dependent inactivation. We will portray a mechanistic view of the events coupling STIM1 to Orai activation based on their structure and biophysics.
authors.affiliation: Institute of Biophysics, University of Linz, Austria. isabella.derler@jku.at
authors.forename: Isabella
authors.initials: I
authors.lastname: Derler
authors.forename: Josef
authors.initials: J
authors.lastname: Madl
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schütz
authors.forename: Christoph
authors.initials: C
authors.lastname: Romanin
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D000071740:ORAI1 Protein; D018384:Oxidative Stress; D055503:Protein Multimerization; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
chemical_list: D001896:Boron Compounds; D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; C109986:2-aminoethoxydiphenyl borate