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2016 ; 310
(8
): C643-62
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Molecular mechanisms of STIM/Orai communication
#MMPMID26825122
Derler I
; Jardin I
; Romanin C
Am J Physiol Cell Physiol
2016[Apr]; 310
(8
): C643-62
PMID26825122
show ga
Ca(2+)entry into the cell via store-operated Ca(2+)release-activated Ca(2+)(CRAC)
channels triggers diverse signaling cascades that affect cellular processes like
cell growth, gene regulation, secretion, and cell death. These store-operated
Ca(2+)channels open after depletion of intracellular Ca(2+)stores, and their main
features are fully reconstituted by the two molecular key players: the stromal
interaction molecule (STIM) and Orai. STIM represents an endoplasmic
reticulum-located Ca(2+)sensor, while Orai forms a highly Ca(2+)-selective ion
channel in the plasma membrane. Functional as well as mutagenesis studies
together with structural insights about STIM and Orai proteins provide a
molecular picture of the interplay of these two key players in the CRAC signaling
cascade. This review focuses on the main experimental advances in the
understanding of the STIM1-Orai choreography, thereby establishing a portrait of
key mechanistic steps in the CRAC channel signaling cascade. The focus is on the
activation of the STIM proteins, the subsequent coupling of STIM1 to Orai1, and
the consequent structural rearrangements that gate the Orai channels into the
open state to allow Ca(2+)permeation into the cell.
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