Selenoprotein K Knockout Mice Exhibit Deficient Calcium Flux in Immune Cells and Impaired Immune Responses
Saguna Verma,FuKun W. Hoffmann,Mukesh Kumar,Zhi Huang,Kelsey Roe,Elizabeth D. Nguyen-Wu,Ann S. Hashimoto,Peter R. Hoffmann +7 more
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TLDR
The results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca2+ flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.Abstract:
Selenoprotein K (Sel K) is a selenium-containing protein for which no function has been identified. We found that Sel K is an endoplasmic reticulum transmembrane protein expressed at relatively high levels in immune cells and is regulated by dietary selenium. Sel K−/− mice were generated and found to be similar to wild-type controls regarding growth and fertility. Immune system development was not affected by Sel K deletion, but specific immune cell defects were found in Sel K−/− mice. Receptor-mediated Ca2+ flux was decreased in T cells, neutrophils, and macrophages from Sel K−/− mice compared with controls. Ca2+-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fcγ receptor-mediated oxidative burst in macrophages were decreased in cells from Sel K−/− mice compared with that in cells from controls. West Nile virus infections were performed, and Sel K−/− mice exhibited decreased viral clearance in the periphery and increased viral titers in brain. Furthermore, West Nile virus-infected Sel K−/− mice demonstrated significantly lower survival (2 of 23; 8.7%) compared with that of wild-type controls (10 of 26; 38.5%). These results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca2+ flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.read more
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Journal ArticleDOI
Selenoproteins: molecular pathways and physiological roles.
TL;DR: Current knowledge about how these unique proteins perform their functions at the molecular level is discussed and new insights into the roles that selenoproteins play in human health are highlighted.
Journal ArticleDOI
The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities
TL;DR: Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells, as well as the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders.
Journal ArticleDOI
Selenium, Selenoproteins, and Immunity
TL;DR: A summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases is presented.
Journal ArticleDOI
Selenium, selenoproteins and the thyroid gland: interactions in health and disease
TL;DR: The baseline selenium status of an individual could constitute the most important parameter modifying the outcome of selenum supplementation, which might primarily disrupt self-amplifying cycles of the endocrine–immune system interface rectifying the interaction of lymphocytes with thyroid autoantigens.
Journal ArticleDOI
Dietary Selenium in Adjuvant Therapy of Viral and Bacterial Infections
TL;DR: A recent review as mentioned in this paper provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (i.e., M. tuberculosis, Helicobacter pylori).
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Anant B. Parekh,Reinhold Penner +1 more
TL;DR: The electrophysiological properties of the prototype store-operated current ICRAC are focused on, the regulatory mechanisms that control it are discussed, and recent advances toward the identification of molecular mechanisms involved in this ubiquitous and important Ca2+ entry pathway are considered.
Journal ArticleDOI
T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes.
TL;DR: It is shown here that lectins known to stimulate T cells raise average [Ca2+]1 approximately twofold within a few minutes, and the co-carcinogen 12-0-tetradecanoylphorbol-13-acetate (TPA) seems to stimulate cell functions normally activated by Ca2+.
Journal ArticleDOI
A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
TL;DR: A p97-interacting membrane protein complex in the mammalian ER that links elimination of misfolded proteins from the endoplasmic reticulum by retro-translocation and its subsequent movement through the membrane by the cytosolic p97 ATPase is identified.
Journal ArticleDOI
STIM1 Clusters and Activates CRAC Channels via Direct Binding of a Cytosolic Domain to Orai1
Chan Young Park,Paul Hoover,Franklin M. Mullins,Priti Bachhawat,Elizabeth D. Covington,Stefan Raunser,Thomas Walz,Thomas Walz,K. Christopher Garcia,Ricardo E. Dolmetsch,Richard S. Lewis +10 more
TL;DR: These studies establish a molecular mechanism for store-operated Ca(2+) entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions.