Numbers count: How STIM and Orai stoichiometry affect store-operated calcium entry.

ABSTRACT: Substantial progress has been made in the past several years in establishing the stoichiometries of STIM and Orai proteins and understanding their influence on store-operated calcium entry. Depletion of ER Ca²⁺ triggers STIM1 to accumulate at ER-plasma membrane junctions where it binds and opens Ca²⁺ release-activated Ca²⁺ (CRAC) channels. STIM1 is a dimer, and release of Ca²⁺ from its two luminal domains is reported to promote their association as well as drive formation of higher-order STIM1 oligomers. The CRAC channel, originally thought to be tetrameric, is now considered to be a hexamer of Orai1 subunits based on crystallographic and electrophysiological studies. STIM1 binding activates CRAC channels in a highly nonlinear way, such that all

SUBMITTER: Yen M 

PROVIDER: S-EPMC6461473 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature