The Novel Endocytic and Phagocytic C-Type Lectin Receptor DCL-1/CD302 on Macrophages Is Colocalized with F-Actin, Suggesting a Role in Cell Adhesion and Migration
Autor: | Masato Kato, Seema A. Khan, E D'Aniello, Derek N.J. Hart, Kylie J. McDonald |
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Rok vydání: | 2007 |
Předmět: |
Podosome
Molecular Sequence Data Immunology CD302 Receptors Cell Surface Biology Cell Line Mice Phagocytosis Cell Movement C-type lectin Cricetinae Cell Adhesion Animals Humans Immunology and Allergy Lectins C-Type Amino Acid Sequence CD93 Conserved Sequence Mannan-binding lectin Mice Inbred BALB C CLEC7A Macrophages Antibodies Monoclonal Membrane Proteins Dendritic Cells Molecular biology Actins Endocytosis Cell biology DC-SIGN biology.protein Sequence Alignment Mannose receptor |
Zdroj: | The Journal of Immunology. 179:6052-6063 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.179.9.6052 |
Popis: | C-type lectin receptors play important roles in mononuclear phagocytes, which link innate and adaptive immunity. In this study we describe characterization of the novel type I transmembrane C-type lectin DCL-1/CD302 at the molecular and cellular levels. DCL-1 protein was highly conserved among the human, mouse, and rat orthologs. The human DCL-1 (hDCl-1) gene, composed of six exons, was located in a cluster of type I transmembrane C-type lectin genes on chromosomal band 2q24. Multiple tissue expression array, RT-PCR, and FACS analysis using new anti-hDCL-1 mAbs established that DCL-1 expression in leukocytes was restricted to monocytes, macrophages, granulocytes, and dendritic cells, although DCL-1 mRNA was present in many tissues. Stable hDCL-1 Chinese hamster ovary cell transfectants endocytosed FITC-conjugated anti-hDCL-1 mAb rapidly (t1/2 = 20 min) and phagocytosed anti-hDCL-1 mAb-coated microbeads, indicating that DCL-1 may act as an Ag uptake receptor. However, anti-DCL-1 mAb-coated microbead binding and subsequent phagocytic uptake by macrophages was ∼8-fold less efficient than that of anti-macrophage mannose receptor (MMR/CD206) or anti-DEC-205/CD205 mAb-coated microbeads. Confocal studies showed that DCL-1 colocalized with F-actin in filopodia, lamellipodia, and podosomes in macrophages and that this was unaffected by cytochalasin D, whereas the MMR/CD206 and DEC-205/CD205 did not colocalize with F-actin. Furthermore, when transiently expressed in COS-1 cells, DCL-1-EGFP colocalized with F-actin at the cellular cortex and microvilli. These data suggest that hDCL-1 is an unconventional lectin receptor that plays roles not only in endocytosis/phagocytosis but also in cell adhesion and migration and thus may become a target for therapeutic manipulation. |
Databáze: | OpenAIRE |
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