Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor from Drosophila melanogaster.

Abstract

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 macrophagelike 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 '251-labeled acetylated low density lipoprotein and mediated its chloroquine-dependent, presumably lysosomal, degradation. Although the broad polyanionic ligand-binding specific

A Novel Role for an Insect Apolipoprotein (Apolipophorin III) in β-1,3-Glucan Pattern Recognition and Cellular Encapsulation Reactions

“…Candidates could include Toll-like receptors or SRs on hemocytes or other cell types, as it is already known that apoLp-III is taken up by granular hemocytes (22), and that Drosophila cells appear to exhibit SR binding of ␤-glucans and other pathogen-associated molecular patterns (PAMPs) and endocytosis of modified LDL (50,51). In mammals, bacterial lipoproteins bind the Toll-like receptor 2, which is itself a pattern recognition receptor (52,53).…”

Role of Macrophage Scavenger Receptors in Hepatic Granuloma Formation in Mice

“…In addition, the elimination of C. parvum by Kupffer cells and monocyte-derived macrophages from the liver of homozygous mutant mice was delayed, and the bacteria remained longer in macrophages, mainly within the hepatic granulomas, compared with the situation in the wild-type mice. Because several types of scavenger receptors besides type I and type II MSR-A are also known, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] we examined the expression of MARCO receptor, macrosialin/CD68, Fc␥ receptor II-B2, and CD36 in the process of the hepatic granuloma formation in homozygous mutant mice and demonstrated the immunohistochemical expression of these proteins and/or their expression at the message level. Among these membrane proteins, MARCO is in the same class as type I and type II MSR-A and is known to be deeply involved in the uptake of bacterial antigens and neutral polysaccharides, and it is expressed in marginal zone macrophages in the spleen and macrophages in lymphatic sinuses of lymph nodes, but not in other tissues, including the liver, in unstimulated normal mice.…”

“…11 These scavenger receptors are divided into three classes: A, B, and C. [1][2][3][4][5][6][7][8][9][10][11] MSR-A and MARCO receptors are included in class A. MSR-A are trimeric membrane glycoproteins consisting of six domains: a C-terminal domain, a collagen-like domain, an ␣-helical coiled coil domain, a spacer domain, a transmembrane domain, and a cytoplasmic domain. 1,2 Although the C-terminal domain is type-specific (ie, different for each type of receptor), the collagen-like domain is common to both receptor types and is important for binding to ligands.…”

Molecular mechanisms of cell death and phagocytosis in Drosophila

“…82,90 Other receptors that may play a role in the recognition of apoptotic cells in the embryo are the Drosophila phosphatidylserine (PS) receptor, 93 and the Drosophila scavenger receptor, DSR-CI. 94 PS exposure is a common feature of apoptotic death, 95 and a recently identified mammalian PS receptor appears to be both necessary and sufficient to promote the engulfment of apoptotic corpses in some cell types. 93 The Drosophila homologue is highly conserved, but its function has not yet been characterized.…”