New developments in the signaling mechanisms of the store-operated calcium entry pathway.
The most ubiquitous pathway for regulated calcium (Ca(2+)) entry into the cells is the store-operated Ca(2+) (SOC) entry pathway (also called capacitative Ca(2+) entry) that is conserved from lower organisms such as yeast, worms, and flies to man. The SOC concept was proposed over two decades ago, and SOC channels are defined by their activation in response to depletion of the internal Ca(2+) stores. Influx through SOC channels is necessary for the replenishment of the Ca(2+) stores and is also involved in cell signaling to the nucleus. Despite intensive investigations, most of which are focusing on transient receptor potential (TRP) channels as molecular candidates for SOC channels, the mechanisms of activation and the identity of the key molecular players participating in this signaling pathway have long remained elusive. In the last 2-3 years, however, the improvements of RNA silencing protocols combined with high throughput platforms have yielded significant breakthroughs, with the identification of Stim1 as the Ca(2+) store sensor and Orai1 (CRACM1) as the pore-forming subunit of the archetypical SOC channel, CRAC. This review summarizes the recent advances in the mechanisms of activation of SOC channels and their molecular composition, with emphasis on the roles of Stim, Orai, and TRP proteins.
Center for Cardiovascular Sciences, Albany Medical College, 47, MC-8, Albany, NY 12208, USA.
Marie
M
Potier
Mohamed
M
Trebak
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050052:TRPC Cation Channels / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000071741:ORAI2 Protein; C514506:ORAI2 protein, human; C522867:Orai3 protein, human; C103530:STIM1 protein, human; C513279:STIM2 protein, human; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050052:TRPC Cation Channels; D010738:Type C Phospholipases