The C-type Lectin Receptor CLECSF8 (CLEC4D) Is Expressed by Myeloid Cells and Triggers Cellular Activation through Syk Kinase*
| Autor: | Ten Feizi, Janet A. Willment, Matti Kimberg, Gordon D. Brown, María Asunción Campanero-Rhodes, Peter Sobieszczuk, Angelina S. Palma, Vandana Gupta, William G. Hornsell, Stella K. Kim, Kevin M. Dennehy, Lisa M. Graham, Reto Guler, Georgia Schäfer, Delyth M. Reid |
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| Přispěvatelé: | Wellcome Trust, National Research Foundation (South Africa), German Academic Exchange Service, University of Cape Town, Medical Research Council (UK), Fundação para a Ciência e a Tecnologia (Portugal), Consejo Superior de Investigaciones Científicas (España), European Commission |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_treatment
Cellular differentiation Cellular Activation Gene Expression Biochemistry Mice 0302 clinical medicine C-type lectin Myeloid Cells Receptors Immunologic Receptor Cells Cultured Respiratory Burst 0303 health sciences CLEC7A Intracellular Signaling Peptides and Proteins food and beverages Cell Differentiation Protein-Tyrosine Kinases Innate Immunity 3. Good health Cell biology Protein Transport Cytokine Organ Specificity Tumor necrosis factor alpha Signal transduction Signal Transduction Recombinant Fusion Proteins Immunology Primary Cell Culture Biology 03 medical and health sciences Phagocytosis medicine Syk Kinase Animals Humans Lectins C-Type Molecular Biology 030304 developmental biology Inflammation Innate immune system Tumor Necrosis Factor-alpha fungi Cell Biology Molecular biology Signaling Mouse Phenotype Protein Structure Tertiary Gene Expression Regulation C-type Lectin 030215 immunology |
| Zdroj: | The Journal of Biological Chemistry Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | 11 pags, 7 figs CLECSF8 is a poorly characterized member of the "Dectin-2 cluster" of C-type lectin receptors and was originally thought to be expressed exclusively by macrophages. We show here that CLECSF8 is primarily expressed by peripheral blood neutrophils and monocytes and weakly by several subsets of peripheral blood dendritic cells. However, expression of this receptor is lost upon in vitro differentiation of monocytes into dendritic cells or macrophages. Like the other members of the Dectin-2 family, which require association of their transmembrane domains with signaling adaptors for surface expression, CLECSF8 is retained intracellularly when expressed in non-myeloid cells. However, we demonstrate that CLECSF8 does not associate with any known signaling adaptor molecule, including DAP10, DAP12, or the FcRγ chain, and we found that the C-type lectin domain of CLECSF8 was responsible for its intracellular retention. Although CLECSF8 does not contain a signaling motif in its cytoplasmic domain, we show that this receptor is capable of inducing signaling via Syk kinase in myeloid cells and that it can induce phagocytosis, proinflammatory cytokine production, and the respiratory burst. These data therefore indicate that CLECSF8 functions as an activation receptor on myeloid cells and associates with a novel adaptor molecule. Characterization of the CLECSF8-deficient mice and screening for ligands using oligosaccharide microarrays did not provide further insights into the physiological function of this receptor. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. This work was funded by the Wellcome Trust, the National Research Foundation, the Deutscher Akademischer Austauschdienst, the University of Cape Town, the UK Research Council Basic Technology Initiative “Glycoar-rays” (GRS/79268), and the UK Medical Research Council. A. S. P is a fellowof the Fundação para a Ciência e Tecnologia (SFRH/BPD/26515/2006, Portugal) and M. A. C. of the Consejo Superior de Investigaciones Cientificas, Programe “Junta para la Ampliación de Estudios” (JaeDoc/098/2011) cofinanced by the Fondo Social Europeo. |
| Databáze: | OpenAIRE |
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