title: Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired 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 Ca(2+) flux was decreased in T cells, neutrophils, and macrophages from Sel K(-/-) mice compared with controls. Ca(2+)-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 Ca(2+) flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Saguna
authors.initials: S
authors.lastname: Verma
authors.forename: FuKun W
authors.initials: FW
authors.lastname: Hoffmann
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.forename: Kelsey
authors.initials: K
authors.lastname: Roe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nguyen-Wu
authors.forename: Ann S
authors.initials: AS
authors.lastname: Hashimoto
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D020013:Calcium Signaling / Q000235:genetics* / Q000276:immunology*; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010538:Peritonitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018000:Receptors, Peptide / Q000378:metabolism; D012643:Selenium / Q000008:administration & dosage / Q000502:physiology; D051140:Selenoproteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C489304:KDELR1 protein, human; D008565:Membrane Proteins; D018000:Receptors, Peptide; D051140:Selenoproteins; D012643:Selenium; D002118:Calcium