Tuning calcium responses

Bogeski, Ivan and Hoth, Markus (2010) Tuning calcium responses. Nature Immunology, 11 (6). p. 469. ISSN doi:10.10.1126/scisignal.2000672

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How calcium signaling, which triggers key functional responses during lymphocyte activation, is influenced by reactive oxygen species is unclear. In Science Signaling, Niemeyer and colleagues show that hydrogen peroxide (H2O2) can oxidize and inhibit the stores-operated calcium channel protein ORAI1 but not the related proteins ORAI2 or ORAI3. This difference in redox sensitivity is due to Cys195 in an extracellular loop of ORAI1 (but absent from the other ORAI proteins) that becomes disulfide-linked after H2O2 exposure. This modification decreases the ORAI-dependent inward Ca2+ flux triggered by release of endoplasmic reticulum stores and activation of the Ca2+ sensor STIM1. Effector T cells are less sensitive than naive T cells to H2O2 oxidation, as expression of ORAI3 is higher in effector cells. Knockdown of ORAI3 in effector T cells increases their sensitivity to oxidizing environments, which leads to lower viability and less interleukin 2 (IL-2) production. How Orai3 expression is upregulated in effector cells remains unknown, but this response is probably critical for effector function at sites of inflammation.

Item Type: Article
Subjects: Medical and Health Sciences > Basic medicine
Medical and Health Sciences > Health sciences
Divisions: Faculty of Medical Science
Depositing User: Ivan Bogeski
Date Deposited: 27 Nov 2012 12:19
Last Modified: 27 Nov 2012 12:19
URI: http://eprints.ugd.edu.mk/id/eprint/2209

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