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Structurally delineating stromal interaction molecules as the endoplasmic reticulum calcium sensors and regulators of calcium release‐activated calcium entry
Author(s) -
Stathopulos Peter B.,
Ikura Mitsuhiko
Publication year - 2009
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2009.00814.x
Subject(s) - endoplasmic reticulum , calcium , microbiology and biotechnology , stim1 , calcium signaling , biology , stromal cell , calcium binding protein , signal transduction , medicine , cancer research
Summary: The endoplasmic reticulum (ER) lumen stores a crucial source of calcium (Ca 2+ ) maintained orders of magnitude higher than the cytosol for the activation of a plethora of cellular responses transmitted in health and disease by a mutually efficient and communicative exchange of Ca 2+ between compartments. A coordination of the Ca 2+ signal is evident in the development of Ca 2+ release‐activated Ca 2+ (CRAC) entry, vital to lymphocyte activation and replenishing of the ER Ca 2+ stores, where modest decreases in ER luminal Ca 2+ induce sustained increases in cytosolic Ca 2+ sourced from steadfast extracellular Ca 2+ supplies. While protein sensors that transduce Ca 2+ signals in the cytosol such as calmodulin are succinctly understood, comparative data on the ER luminal Ca 2+ sensors is only recently coming to light with the discovery that stromal interaction molecules (STIMs) sense variations in ER stored Ca 2+ levels in the functional regulation of plasma membrane Orai proteins, the major component of CRAC channel pores. Drawing from data on the role of STIMs in the modulation of CRAC entry, this review illustrates the structural features that delimit the functional characteristics of ER Ca 2+ sensors relative to well known cytoplasmic Ca 2+ sensors.