TY - JOUR
T1 - New developments in the signaling mechanisms of the store-operated calcium entry pathway
AU - Potier, Marie
AU - Trebak, Mohamed
N1 - Funding Information:
Work in the authors’ laboratory is supported by start up funds from the Albany Medical College, NY and by an early career NIH grant to M.T. (K22ES014729).
PY - 2008/11
Y1 - 2008/11
N2 - The most ubiquitous pathway for regulated calcium (Ca2+) entry into the cells is the store-operated Ca2+ (SOC) entry pathway (also called capacitative Ca2+ 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 Ca2+ stores. Influx through SOC channels is necessary for the replenishment of the Ca2+ 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 Ca2+ 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.
AB - The most ubiquitous pathway for regulated calcium (Ca2+) entry into the cells is the store-operated Ca2+ (SOC) entry pathway (also called capacitative Ca2+ 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 Ca2+ stores. Influx through SOC channels is necessary for the replenishment of the Ca2+ 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 Ca2+ 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.
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U2 - 10.1007/s00424-008-0533-2
DO - 10.1007/s00424-008-0533-2
M3 - Review article
C2 - 18536932
AN - SCOPUS:56649103777
SN - 0031-6768
VL - 457
SP - 405
EP - 415
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
IS - 2
ER -