Journal
CELL CALCIUM
Volume 42, Issue 2, Pages 173-182Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2007.03.009
Keywords
calcium signals; calcium entry channels; store-operated calcium entry; orai1; STIM1; STIM2
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Ca2+ signals are universal among cells in regulating a spectrum of cellular responses. Phospholipase C-coupled receptors activate two components of Ca (2+) signals-rapid Ca2+ release from ER stores, followed by slower Ca 2+ entry from outside the cell. The coupling process between ER and PM to mediate this store-operated Ca2+ entry process remained until recently a molecular mystery. The recent discovery of the necessity for STIM I and Orai proteins in this process has provided crucial information on the coupling mechanism between stores and PM Ca2+ entry. STIM1 is a single spanning membrane protein with an unpaired Ca2+ binding EF-hand and appears to function as the sensor of ER luminal Ca2+, and, through redistribution in the ER, transduces information directly to the PM. Orai I is a tetra-spanning PM protein and functions as the highly Ca2+-selective channel in the PM that is gated through interactions with the store-activated ER Ca2+ sensor. Recent evidence shows the two proteins together are necessary and sufficient for the function of store-operated Ca2+ entry. However, many questions arise about how and where the interactions of the STIM I and Orai I proteins occur within cells. Here we discuss recent information and ideas about the coupling between these proteins that leads to store-operated channel activation. (C) 2007 Elsevier Ltd. All rights reserved.
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