Research ArticleCalcium signaling

Cell type–specific glycosylation of Orai1 modulates store-operated Ca2+ entry

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Science Signaling  08 Mar 2016:
Vol. 9, Issue 418, pp. ra25
DOI: 10.1126/scisignal.aaa9913

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Sugary coating on Orai1

Glycosylation is the addition of sugars to proteins and the chemical modification of these sugars to form highly complex structures. Glycosylation can affect protein stability, protein-protein interactions, and protein function. Human Orai1 is the channel-forming subunit of a complex that mediates calcium entry into cells when calcium in the endoplasmic reticulum becomes depleted (a process called SOCE). Orai1 has a single N-glycosylation site. Dörr et al. found that cells, including several types of immune cells, exposed to conditions that altered Orai1 glycosylation specifically or cellular glycosylation globally exhibited cell-specific effects on SOCE. In many cases, disruption of glycosylation enhanced SOCE without affecting Orai1 abundance or presence at the cell surface, suggesting that glycosylation limited Orai1 activity. Excess SOCE and altered glycosylation are associated with various immune diseases and differences in Orai1 function may be an important molecular connection between these two cellular events.

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