Molecular Cloning and Functional Characterization of a Human Scavenger Receptor with C-Type Lectin (SRCL), a Novel Member of a Scavenger Receptor Family

Nakamura, Kenji; Funakoshi, Hiroshi; Miyamoto, Kazuhito; Tokunaga, Fumio; Nakamura, Toshikazu

doi:10.1006/bbrc.2000.4210

Cited by 101 publications

(94 citation statements)

References 35 publications

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“…CL-12 was originally identified and characterized from placenta and liver as a membrane-anchored molecule functioning as an endocytic receptor present on vascular endothelial cells (10,17). It has previously been shown that macrophage-specific scavenger receptor/collagen-like domain 163, which mediates the internalization of hemoglobin-haptoglobin complexes by macrophages, can be shed as a soluble form from the cell surface by activation of TLR, cross-linking of the Fcg receptor or oxidative stress, and so on during inflammation and macrophage activation (25).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, CL-11 has recently been shown to be an LP-activating molecule associated with the LP-associated serine proteases (MASPs) in addition to MBL and the ficolins (16). Different from the other novel collectins, CL-12 was originally defined as scavenger receptor C-type lectin because it shares structural and functional similarities with type A scavenger receptor and collectins (10,17). As a transmembrane scavenger receptor, CL-12 is mainly localized in vascular endothelial cells in general, but in particular in umbilical cord endothelial cells (18).…”

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confidence: 99%

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Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway

Jie

Hein

Munthe-Fog

et al. 2015

The Journal of Immunology

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Soluble defense collagens including the collectins play important roles in innate immunity. Recently, a new member of the collectin family named collectin-12 (CL-12 or CL-P1) has been identified. CL-12 is highly expressed in umbilical cord vascular endothelial cells as a transmembrane receptor and may recognize certain bacteria and fungi, leading to opsonophagocytosis. However, based on its structural and functional similarities with soluble collectins, we hypothesized the existence of a fluid-phase analog of CL-12 released from cells, which may function as a soluble pattern-recognition molecule. Using recombinant CL-12 full length or CL-12 extracellular domain, we determined the occurrence of soluble CL-12 shed from in vitro cultured cells. Western blot showed that soluble recombinant CL-12 migrated with a band corresponding to ∼120 kDa under reducing conditions, whereas under nonreducing conditions it presented multimeric assembly forms. Immunoprecipitation and Western blot analysis of human umbilical cord plasma enabled identification of a natural soluble form of CL-12 having an electrophoretic mobility pattern close to that of shed soluble recombinant CL-12. Soluble CL-12 could recognize Aspergillus fumigatus partially through the carbohydrate-recognition domain in a Ca2+-independent manner. This led to activation of the alternative pathway of complement exclusively via association with properdin on A. fumigatus as validated by detection of C3b deposition and formation of the terminal complement complex. These results demonstrate the existence of CL-12 in a soluble form and indicate a novel mechanism by which the alternative pathway of complement may be triggered directly by a soluble pattern-recognition molecule.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway

Jie

Hein

Munthe-Fog

et al. 2015

The Journal of Immunology

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“…The SRs are classified into several subgroups, of which class A SRs have primarily been associated with innate immunity. This class consists of five members: SR-A (SR-AI, -II, and -III/ SCARA1) (3,4), MARCO (macrophage receptor with collagenous domain)/SCARA2 (5), CSR1 (cellular stress response 1) and CSR2/SCARA3 (6), SRCL (scavenger receptor with C-type lectin) I and II/SCARA4 (7,8), and Tesr (testis-expressed scavenger receptor)/SCARA5 (class A scavenger receptor 5) (9, 10). All of these are trimeric type II membrane proteins with a similar predicted tertiary structure consisting of a short intracellular domain, a transmembrane domain, and a large extracellular domain with an ␣-helical coiled-coil domain, a triple-helical collagenous domain, and a C-terminal cysteine-rich domain.…”

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confidence: 99%

“…In addition, the C-terminal cysteine-rich domain can be either a C-type lectin-like domain, as it is in SRCL, or a scavenger receptor cysteine-rich (SRCR) domain, present in SR-AI, MARCO, and SCARA5. The splice variants, SR-AII/III, SRCL II, and CSR, are missing the cysteine-rich domain (3)(4)(5)(6)(7)(8)(9)(10).…”

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confidence: 99%

Crystal Structure of the Cysteine-rich Domain of Scavenger Receptor MARCO Reveals the Presence of a Basic and an Acidic Cluster That Both Contribute to Ligand Recognition

Ojala

Pikkarainen

Tuuttila

et al. 2007

Journal of Biological Chemistry

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MARCO is a trimeric class A scavenger receptor of macrophages and dendritic cells that recognizes polyanionic particles and pathogens. The distal, scavenger receptor cysteine-rich (SRCR) domain of the extracellular part of this receptor has been implicated in ligand binding. To provide a structural basis for understanding the ligand-binding mechanisms of MARCO, we have determined the crystal structure of the mouse MARCO SRCR domain. The recombinant SRCR domain purified as monomeric and dimeric forms, and their structures were determined at 1.78 and 1.77 Å resolution, respectively. The monomer has a compact globular fold with a twisted five-stranded antiparallel ␤-sheet and a long loop covering a single ␣-helix, whereas the dimer is formed via ␤-strand swapping of two monomers, thus containing a large eight-stranded ␤-sheet. Calculation of the surface electrostatic potential revealed that the ␤-sheet region with several arginines forms a basic cluster. Unexpectedly, an acidic cluster was found in the long loop region. In the monomer, the acidic cluster is involved in metal ion binding. Studies with cells expressing various SRCR domain mutants showed that all of the arginines of the basic cluster are involved in ligand binding, suggesting a cooperative binding mechanism. Ligand binding is also dependent on the acidic cluster and Ca 2؉ ions whose depletion appears to affect ligand binding at least by modulating the electrostatic potential or relative domain orientation. We propose that the SRCR domain dimerization can contribute to the recognition of large ligands by providing a means for the MARCO receptor oligomerization.MARCO belongs to a diverse group of scavenger receptors (SRs) 3 expressed by macrophages, dendritic cells, and certain endothelial cells (1). These germ line-encoded receptors, also known as pattern recognition receptors due to their ability to recognize conserved pathogen-associated molecular patterns, are considered as an important part of innate immunity, the evolutionarily conserved, first line host defense mechanism. In addition to pathogen-associated molecular patterns, a long list of SR ligands, often polyanionic in nature, includes pollution particles, polyribonucleotides, bacterial lipopolysaccharides, modified host molecules such as oxidized low density lipoprotein (LDL), and unmodified endogenous proteins (1, 2). The SRs are classified into several subgroups, of which class A SRs have primarily been associated with innate immunity. This class consists of five members: SR-A (SR-AI, -II, and -III/ SCARA1) (3, 4), MARCO (macrophage receptor with collagenous domain)/SCARA2 (5), CSR1 (cellular stress response 1) and CSR2/SCARA3 (6), SRCL (scavenger receptor with C-type lectin) I and II/SCARA4 (7, 8), and Tesr (testis-expressed scavenger receptor)/SCARA5 (class A scavenger receptor 5) (9, 10). All of these are trimeric type II membrane proteins with a similar predicted tertiary structure consisting of a short intracellular domain, a transmembrane domain, and a large extracellular domain with...

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“…COLEC12 is the only member of the Collectin scavenger receptor family that is expressed as a cell surface transmembrane protein, and its ECD contains coiled-coil, collagen-like, and C-type lectin/carbohydrate domains (32). COLEC12 is expressed in vascular endothelial cells and monocytes and mediates the uptake of oxidized low density lipoproteins and microbes (32,33). Interestingly, Collectins have been shown to interact with other inhibitory receptors such as signal regulatory protein ␣ to modulate lung pathophysiology (41).…”

Section: Discussionmentioning

confidence: 99%

Evolutionarily Conserved Paired Immunoglobulin-like Receptor α (PILRα) Domain Mediates Its Interaction with Diverse Sialylated Ligands

Sun¹,

Senger²,

Baginski³

et al. 2012

Journal of Biological Chemistry

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Background: PILR␣ is an inhibitory receptor predominantly expressed in myeloid cells. Results: NPDC1 and COLEC12 are novel PILR␣ ligands. PILR␣ arginine residues 133 (mouse) and 126 (human) are critical contact residues. Conclusion: PILR␣/ligand interactions involve a conserved domain in PILR␣ and a sialylated protein domain in the ligand. Significance: PILR␣ interacts with various ligands to alter myeloid cell function.

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Molecular Cloning and Functional Characterization of a Human Scavenger Receptor with C-Type Lectin (SRCL), a Novel Member of a Scavenger Receptor Family

Cited by 101 publications

References 35 publications

Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway

Soluble Collectin-12 (CL-12) Is a Pattern Recognition Molecule Initiating Complement Activation via the Alternative Pathway

Crystal Structure of the Cysteine-rich Domain of Scavenger Receptor MARCO Reveals the Presence of a Basic and an Acidic Cluster That Both Contribute to Ligand Recognition

Evolutionarily Conserved Paired Immunoglobulin-like Receptor α (PILRα) Domain Mediates Its Interaction with Diverse Sialylated Ligands

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