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

Dörr, Kathrin; Kilch, Tatiana; Kappel, Sven; Alansary, Dalia; Schwär, Gertrud; Niemeyer, Barbara A; Peinelt, Christine (2016). Cell type-specific glycosylation of Orai1 modulates store-operated Ca2+ entry. Science signaling, 9(418), ra25. American Association for the Advancement of Science 10.1126/scisignal.aaa9913

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N-glycosylation of cell surface proteins affects protein function, stability, and interaction with other proteins. Orai channels, which mediate store-operated Ca(2+) entry (SOCE), are composed of N-glycosylated subunits. Upon activation by Ca(2+) sensor proteins (stromal interaction molecules STIM1 or STIM2) in the endoplasmic reticulum, Orai Ca(2+) channels in the plasma membrane mediate Ca(2+) influx. Lectins are carbohydrate-binding proteins, and Siglecs are a family of sialic acid-binding lectins with immunoglobulin-like repeats. Using Western blot analysis and lectin-binding assays from various primary human cells and cancer cell lines, we found that glycosylation of Orai1 is cell type-specific. Ca(2+) imaging experiments and patch-clamp experiments revealed that mutation of the only glycosylation site of Orai1 (Orai1N223A) enhanced SOCE in Jurkat T cells. Knockdown of the sialyltransferase ST6GAL1 reduced α-2,6-linked sialic acids in the glycan structure of Orai1 and was associated with increased Ca(2+) entry in Jurkat T cells. In human mast cells, inhibition of sialyl sulfation altered the N-glycan of Orai1 (and other proteins) and increased SOCE. These data suggest that cell type-specific glycosylation influences the interaction of Orai1 with specific lectins, such as Siglecs, which then attenuates SOCE. In summary, the glycosylation state of Orai1 influences SOCE-mediated Ca(2+) signaling and, thus, may contribute to pathophysiological Ca(2+) signaling observed in immune disease and cancer.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Kappel, Sven, Peinelt, Christine


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




American Association for the Advancement of Science




Christine Peinelt

Date Deposited:

30 May 2017 15:40

Last Modified:

05 Dec 2022 15:03

Publisher DOI:


PubMed ID:






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