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PMID:21220695

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Citation

Verma, S, Hoffmann, FW, Kumar, M, Huang, Z, Roe, K, Nguyen-Wu, E, Hashimoto, AS and Hoffmann, PR (2011) Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses. J. Immunol. 186:2127-37

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.

Links

PubMed PMC3088479 Online version:10.4049/jimmunol.1002878

Keywords

Animals; Calcium/antagonists & inhibitors; Calcium/physiology; Calcium Signaling/genetics; Calcium Signaling/immunology; Cell Migration Inhibition/genetics; Cell Migration Inhibition/immunology; Disease Models, Animal; Endoplasmic Reticulum/immunology; Endoplasmic Reticulum/metabolism; Endoplasmic Reticulum/pathology; Gene Expression Regulation/immunology; Humans; Lymph Nodes/immunology; Lymph Nodes/metabolism; Lymph Nodes/pathology; Membrane Proteins/biosynthesis; Membrane Proteins/deficiency; Membrane Proteins/genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Peritonitis/genetics; Peritonitis/immunology; Peritonitis/pathology; Receptors, Peptide/metabolism; Selenium/administration & dosage; Selenium/physiology; Selenoproteins/biosynthesis; Selenoproteins/deficiency; Selenoproteins/genetics; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; T-Lymphocytes/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SELK

acts_upstream_of_or_within

GO:0030335: positive regulation of cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4941878

P

  • regulates_o_results_in_movement_of:(CL:0000775)

Seeded From UniProt

complete

MOUSE:SELK

acts_upstream_of_or_within

GO:0006816: calcium ion transport

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4941878

P

Seeded From UniProt

complete

MOUSE:SELK

located_in

GO:0005789: endoplasmic reticulum membrane

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:35523)

Seeded From UniProt

complete

MOUSE:SELK

acts_upstream_of_or_within

GO:2000406: positive regulation of T cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4941878

P

  • regulates_o_results_in_movement_of:(CL:0000084)

Seeded From UniProt

complete

MOUSE:SELK

acts_upstream_of_or_within

GO:0045728: respiratory burst after phagocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4941878

P

  • occurs_in:(CL:0002476)

Seeded From UniProt

complete

MOUSE:SELK

acts_upstream_of_or_within

GO:0042102: positive regulation of T cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4941878

P

Seeded From UniProt

complete

MOUSE:SELK

involved_in

GO:0002230: positive regulation of defense response to virus by host

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SELK

involved_in

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SELK

involved_in

GO:0032755: positive regulation of interleukin-6 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SELK

involved_in

GO:0032722: positive regulation of chemokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SELK

NOT|involved_in

GO:2001256: regulation of store-operated calcium entry

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SELK

involved_in

GO:0050848: regulation of calcium-mediated signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SELK

involved_in

GO:0071639: positive regulation of monocyte chemotactic protein-1 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SELK

located_in

GO:0005789: endoplasmic reticulum membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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