title: Partial unfolding and oligomerization of stromal interaction molecules as an initiation mechanism of store operated calcium entry.
abstract: Spatiotemporally discrete cytoplasmic Ca2+ fluctuations are fundamental eukaryotic signals in myriad physiological and pathophysiological functions. Store-operated Ca2+ entry is the process whereby a decrease in endoplasmic reticulum (ER) luminal Ca2+ levels activates Ca2+ release activated calcium (CRAC) channels on the plasma membrane (PM), providing a sustained Ca2+ elevation to the cytoplasm and ultimately replenishing the ER lumen Ca2+ supply. Stromal interaction molecules (STIMs) are the Ca2+ sensors of the ER lumen, which macromolecularly couple depleted ER Ca2+ to the assembly and opening of PM CRAC channels. The considerable stability difference caused by Ca2+ loading and depletion within the luminal portion of STIMs modulates intramolecular cytoplasmic domain interactions essential to the assembly of PM CRAC channels. Thus, the action of the entire complex is tightly regulated through the Ca2+ sensitivity of luminal STIM domains. Recent structural and biochemical studies suggest that partial unfolding - coupled oligomerization of STIMs is a crucial step in CRAC channel activation. Based on these and other published data, this minireview discusses what is currently known about the molecular mechanism of ER Ca2+ sensing by STIMs.
authors.affiliation: Division of Signaling Biology and Department of Medical Biophysics, Ontario Cancer Institute and University of Toronto, Toronto Medical Discovery Tower, MaRS Centre, 101 College St., Toronto, ON M5G 1L7, Canada.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Stathopulos
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Ikura
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D017510:Protein Folding
chemical_list: D008565:Membrane Proteins; D002118:Calcium