Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor from Drosophila melanogaster.
Mammalian class A macrophage-specific scavenger receptors (SR-A) exhibit unusually broad binding specificity for a wide variety of polyanionic ligands. The properties of these receptors suggest that they may be involved in atherosclerosis and host defense. We have previously observed a similar receptor activity in Drosophila melanogaster embryonic macrophages and in the Drosophila macrophage-like Schneider L2 cell line. Expression cloning was used to isolate from L2 cells a cDNA that encodes a third class (class C) of scavenger receptor, Drosophila SR-CI (dSR-CI). dSR-CI expression was restricted to macrophages/hemocytes during embryonic development. When expressed in mammalian cells, dSR-CI exhibited high affinity and saturable binding of 125I-labeled acetylated low density lipoprotein and mediated its chloroquine-dependent, presumably lysosomal, degradation. Although the broad polyanionic ligand-binding specificity of dSR-CI was similar to that of SR-A, their predicted protein sequences are not similar. dSR-CI is a 609-residue type I integral membrane protein containing several well-known sequence motifs, including two complement control protein (CCP) domains and somatomedin B, MAM, and mucin-like domains. Macrophage scavenger receptors apparently mediate important, well-conserved functions and may be pattern-recognition receptors that arose early in the evolution of host-defense mechanisms. Genetic and physiologic analysis of dSR-CI function in Drosophila should provide further insights into the roles played by scavenger receptors in host defense and development.
Pearson
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A
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Lux
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A
Krieger
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D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D016466:CHO Cells; D003001:Cloning, Molecular; D016384:Consensus Sequence; D006224:Cricetinae; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000276:immunology*; D004625:Embryo, Nonmammalian / Q000276:immunology; D015870:Gene Expression; D017403:In Situ Hybridization; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D051124:Scavenger Receptors, Class C; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D029721:Drosophila Proteins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D051124:Scavenger Receptors, Class C; C495127:Sr-CI protein, Drosophila; C495128:Sr-CIII protein, Drosophila; C032629:acetyl-LDL