Research ArticleCell Biology

Cholesterol modulates Orai1 channel function

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Science Signaling  26 Jan 2016:
Vol. 9, Issue 412, pp. ra10
DOI: 10.1126/scisignal.aad7808

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Orai1 senses cholesterol

Calcium in cells is stored in various compartments and released to initiate various cellular processes and signaling cascades. Orai proteins are the channel component of a complex that mediates the CRAC current, which mediates calcium influx into cells in response to the depletion of calcium from intracellular stores. Derler et al. found that cholesterol bound to Orai1, suppressing its activity and calcium influx. In mast cells, cholesterol depletion enhanced CRAC currents and degranulation, a process that releases inflammatory mediators such as histamine and requires increased intracellular calcium. Thus, cholesterol reduces the activity of Orai1 and calcium influx through this channel.

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