A Drosophila Gene Encoding an Epithelial Membrane Protein with Homology to CD36/LIMP II

Hart, Karen; Wilcox, Michael

doi:10.1006/jmbi.1993.1580

Cited by 63 publications

(36 citation statements)

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“…Even though LmpB is more distantly related to both LmpA and LmpC, it shares with the other two proteins some important structural features, such as the large N-glycosylated intravesicular domain that is flanked by hydrophobic domains near the carboxyl and the amino termini. The overall topology of these proteins is apparently highly conserved and corresponds to the hairpin topology found in CD36/LIMPII family proteins from higher eukaryotes (24,47,49,50). We could experimentally confirm both the N-glycosylation and the proposed topology of the products for all three different lmp genes.…”

Section: Fig 4 Developmental Regulationsupporting

confidence: 56%

Characterization of CD36/LIMPII Homologues inDictyostelium discoideum

Janssen¹,

Rost²,

Eichinger³

et al. 2001

Journal of Biological Chemistry

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The CD36/LIMPII family is ubiquitously expressed in higher eukaryotes and consists of integral membrane proteins that have in part been characterized as cell adhesion receptors, scavenger receptors, or fatty acid transporters. However, no physiological role has been defined so far for the members of this family that localize specifically to vesicular compartments rather than to the cell surface, namely lysosomal integral membrane protein type II (LIMPII) from mammals and LmpA from the amoeba Dictyostelium discoideum. LmpA, the first described CD36/LIMPII homologue from lower eukaryotes, has initially been identified as a suppressor of the profilin-minus phenotype. We report the discovery and initial characterization of two new CD36/LIMPIIrelated proteins, both of which share several features with LmpA: (i) their size is considerably larger than that of the CD36/LIMPII proteins from higher eukaryotes; (ii) they show the characteristic "hairpin" topology of this protein family; (iii) they are heavily N-glycosylated; and (iv) they localize to vesicular structures of putative endolysosomal origin. However, they show intriguing differences in their developmental regulation and exhibit different sorting signals of the di-leucine or tyrosinetype in their carboxyl-terminal tail domains. These features make them promising candidates as a paradigm for the study of the function and evolution of the as yet poorly understood CD36/LIMPII proteins.

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Section: Fig 4 Developmental Regulationsupporting

confidence: 56%

Characterization of CD36/LIMPII Homologues inDictyostelium discoideum

Janssen¹,

Rost²,

Eichinger³

et al. 2001

Journal of Biological Chemistry

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“…CD36 developed as part of the innate immune system, and the scavenger function of CD36 is evolutionarily conserved (35,36). Aside from its function as a receptor for OxLDL, CD36 is thought to play an important role in the recognition and removal of cells undergoing programmed cell death and of pathogens during infection, in cooperation with the phosphatidylserine receptor or the ␣ v ␤ 3 integrin (7,37).…”

Section: Discussionmentioning

confidence: 99%

Phosphocholine as a pattern recognition ligand for CD36

Boullier

Friedman

Harkewicz

et al. 2005

Journal of Lipid Research

109

108

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We have previously shown that CD36 recognizes oxidation products of phospholipids on oxidized LDL (OxLDL) such as 1-palmitoyl-2-(5 -oxovaleroyl)-sn -glycero-3-phosphocholine (POVPC). The current study was designed to examine whether the phosphocholine (PC) headgroup in POVPC constitutes an obligatory binding target for CD36. To examine the contribution of PC in the binding of POVPC to CD36, we used well-defined synthetic oxidized phospholipids (OxPLs) cross-linked to BSA or to a hexapeptide. The OxPL adducts were then tested for their ability to bind to CD36-transfected cells and for their ability to inhibit OxLDL binding to CD36. Mounting evidence implicates oxidized low density lipoprotein (OxLDL) in the pathogenesis of atherosclerosis. The oxidative modifications are presumed to occur after the entry of plasma LDL into the intima and are catalyzed by the cellular constituents of the arterial wall. Although clearance of the highly cytotoxic OxLDL may protect the surrounding tissue from damage, the unregulated uptake of OxLDL by macrophages within the arterial wall leads to the formation of lipid-laden foam cells and the development of the fatty streak, the hallmark of early atherosclerotic lesions. The recognition and uptake of OxLDL by macrophages is mediated by specific cell surface scavenger receptors, including CD36, a class B scavenger receptor (1). CD36 is a heavily glycosylated protein with broad ligand specificity, a characteristic of pattern recognition receptors. It binds long-chain fatty acids (2), anionic phospholipids (3), ␤ -amyloid (4), advanced glycation end products (5), and OxLDL (1). It also functions in the recognition and removal of Plasmodium falciparum -infected erythrocytes (6) and apoptotic cells (7). It serves as the primary receptor for platelet adhesion to collagen (8) and may mediate the antiangiogenic activity of thrombospondin (9).Recent data derived from CD36-deficient mice support an important role of CD36 in foam cell formation and atherogenesis. A significant decrease in binding and degradation of OxLDL was observed in macrophages from null mice compared with those from control mice (10). Similarly, macrophages from CD36-deficient patients were less capable of binding and degrading OxLDL and accumulated less cholesteryl ester than macrophages from control subjects (11). The relative contribution of scavenger receptors in the uptake of OxLDL was further addressed in mice lacking both scavenger receptor A and CD36 (12). Binding and uptake studies demonstrated that scavenger receptor A and CD36 were the principal macrophage receptors responsible for the binding of OxLDL and the accumulation of cholesteryl ester derived from modified lipoproteins. Consistent with a principal pathogenic role of scavenger receptors in atherogenesis, the targeted disrup-

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“…In the two cases examined (posi- SR-BI is a member of the CD36 superfamily of proteins that includes the mammalian proteins CD36 (36,37) and LIMPII (a lysosomal integral membrane protein (38)), two Drosophila melanogaster proteins, emp (39) and croquemort (a hemocyte/ macrophage receptor) (40,41), SnmP-1 (a silk moth olfatory neuron membrane protein) (42), and one putative Caenorhabditis elegans protein (GenBank TM Z54270). Table I shows the degree of conservation of the 11 N-linked Asn-X (not Pro)-Ser/ Thr sites in the 22 sequences of these proteins, identified using Psi-blast (43).…”

Section: Discussionmentioning

confidence: 99%

Identification of the N-Linked Glycosylation Sites on the High Density Lipoprotein (HDL) Receptor SR-BI and Assessment of Their Effects on HDL Binding and Selective Lipid Uptake

Viñals¹,

Vasile

et al. 2003

Journal of Biological Chemistry

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The murine class B, type I scavenger receptor mSR-BI, a high density lipoprotein (HDL) receptor that mediates selective uptake of HDL lipids, contains 11 potential N-linked glycosylation sites and unknown numbers of both endoglycosidase H-sensitive and -resistant oligosaccharides. We have examined the consequences of mutating each of these sites (Asn 3 Gln or Thr 3 Ala) on post-translational processing of mSR-BI, cell surface expression, and HDL binding and lipid transport activities. All 11 sites were glycosylated; however, disruption of only two (Asn-108 and Asn-173) substantially altered expression and function. There was very little detectable post-translational processing of these two mutants to endoglycosidase H resistance and very low cell surface expression, suggesting that oligosaccharide modification at these sites apparently plays an important role in endoplasmic reticulum folding and/or intracellular transport. Strikingly, although the low levels of the 108 and 173 mutants that were expressed on the cell surface exhibited a marked reduction in their ability to transfer lipids from HDL to cells, they nevertheless bound nearly normal amounts of HDL. Indeed, the affinity of 125 I-HDL binding to the 173 mutant was similar to that of the wild-type receptor. Thus, N-linked glycosylation can influence both the intracellular transport and lipid-transporter activity of SR-BI. The ability to uncouple the HDL binding and lipid transport activities of mSR-BI by in vitro mutagenesis should provide a powerful tool for further analysis of the mechanism of SR-BI-mediated selective lipid uptake. Scavenger receptor class B, type I, SR-BI,1 is a 509-residue, ϳ82-kDa integral membrane cell surface glycoprotein of the CD36 superfamily that was the first high density lipoprotein (HDL) receptor to be characterized in detail (1, 2). SR-BI helps control the structure and metabolism of HDL by mediating the transport of lipids from HDL to cells. The mechanism by which SR-BI mediates this lipid transport differs from the classic LDL receptor pathway of endocytosis, in which the entire lipoprotein is internalized via coated pits and subsequently hydrolyzed by lysosomal enzymes (3). Instead, HDL binds to SR-BI, lipids of HDL (primarily neutral lipids such as cholesteryl esters in the core of the particle) are transported into the cells, and the lipid-depleted particle is released into the extracellular space (1, 2, 4, 5). This mechanism is called selective lipid uptake (2, 4, 5). Numerous studies indicate that SR-BI-mediated selective lipid uptake is a two-step process involving productive binding of HDL (1, 6, 7) followed by bindingdependent lipid transfer. In addition to mediating selective lipid uptake, SR-BI can mediate cholesterol efflux from cells to HDL (8) via a binding-dependent process (6, 7, 9) (however see In vivo analyses of the function of SR-BI, primarily using SR-BI homozygous null mice (11, 12) and murine hepatic overexpression of SR-BI transgenes (13-18), have shown that SR-BI can profoundly influence several ph...

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A Drosophila Gene Encoding an Epithelial Membrane Protein with Homology to CD36/LIMP II

Cited by 63 publications

References 0 publications

Characterization of CD36/LIMPII Homologues inDictyostelium discoideum

Characterization of CD36/LIMPII Homologues inDictyostelium discoideum

Phosphocholine as a pattern recognition ligand for CD36

Identification of the N-Linked Glycosylation Sites on the High Density Lipoprotein (HDL) Receptor SR-BI and Assessment of Their Effects on HDL Binding and Selective Lipid Uptake

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