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Scavenger receptor structure and function in health and disease.

Zani IA, Stephen SL, Mughal NA, Russell D, Homer-Vanniasinkam S, Wheatcroft SB, Ponnambalam S - Cells (2015)

Bottom Line: These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence.Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens.Here, we review our current understanding of SR structure and function implicated in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.

ABSTRACT
Scavenger receptors (SRs) are a 'superfamily' of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.

No MeSH data available.


Related in: MedlinePlus

Schematic overview of ligand-stimulated SR signal transduction. OxLDL-stimulated activation of intracellular signaling pathways is exemplified by SR-A, SR-B2 (CD36) and SR-E1 (LOX-1). Different endocytosis pathway are denoted 1–3 (1) caveolae-mediated uptake, (2) lipid-raft dependent uptake, and (3) clathrin-independent pathway.
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cells-04-00178-f002: Schematic overview of ligand-stimulated SR signal transduction. OxLDL-stimulated activation of intracellular signaling pathways is exemplified by SR-A, SR-B2 (CD36) and SR-E1 (LOX-1). Different endocytosis pathway are denoted 1–3 (1) caveolae-mediated uptake, (2) lipid-raft dependent uptake, and (3) clathrin-independent pathway.

Mentions: SR-A1 can undergo internalization from the plasma membrane via clathrin-dependent endocytosis (CDE) or clathrin-independent endocytosis (CIE) routes. SR-A1 binding to modified LDL is linked to CDE via recognition of a cytoplasmic dileucine motif [12]. One such example of CIE is caveolae-mediated uptake: SR-A1-ligand internalization via this route stimulates apoptosis [13] (Figure 2). In antigen-presenting cells, SR-A1-mediated pathogen uptake involves phagocytosis by a lipid raft-dependent mechanism [14]. SR-A1- mice display 50-70% reduction in acetylated LDL (AcLDL) and OxLDL uptake with a corresponding size reduction in atherosclerotic lesions [15,16]. Nonetheless, there is agreement that gene knockouts cause reduced pro-inflammatory responses, macrophage apoptosis and cellular necrosis with better stabilization of atherosclerotic plaques [17,18]. Interestingly, viral gene therapy promotes soluble SR-A1 expression and secretion decreased modified LDL accumulation, foam cell incidence and atherosclerosis [19].


Scavenger receptor structure and function in health and disease.

Zani IA, Stephen SL, Mughal NA, Russell D, Homer-Vanniasinkam S, Wheatcroft SB, Ponnambalam S - Cells (2015)

Schematic overview of ligand-stimulated SR signal transduction. OxLDL-stimulated activation of intracellular signaling pathways is exemplified by SR-A, SR-B2 (CD36) and SR-E1 (LOX-1). Different endocytosis pathway are denoted 1–3 (1) caveolae-mediated uptake, (2) lipid-raft dependent uptake, and (3) clathrin-independent pathway.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493455&req=5

cells-04-00178-f002: Schematic overview of ligand-stimulated SR signal transduction. OxLDL-stimulated activation of intracellular signaling pathways is exemplified by SR-A, SR-B2 (CD36) and SR-E1 (LOX-1). Different endocytosis pathway are denoted 1–3 (1) caveolae-mediated uptake, (2) lipid-raft dependent uptake, and (3) clathrin-independent pathway.
Mentions: SR-A1 can undergo internalization from the plasma membrane via clathrin-dependent endocytosis (CDE) or clathrin-independent endocytosis (CIE) routes. SR-A1 binding to modified LDL is linked to CDE via recognition of a cytoplasmic dileucine motif [12]. One such example of CIE is caveolae-mediated uptake: SR-A1-ligand internalization via this route stimulates apoptosis [13] (Figure 2). In antigen-presenting cells, SR-A1-mediated pathogen uptake involves phagocytosis by a lipid raft-dependent mechanism [14]. SR-A1- mice display 50-70% reduction in acetylated LDL (AcLDL) and OxLDL uptake with a corresponding size reduction in atherosclerotic lesions [15,16]. Nonetheless, there is agreement that gene knockouts cause reduced pro-inflammatory responses, macrophage apoptosis and cellular necrosis with better stabilization of atherosclerotic plaques [17,18]. Interestingly, viral gene therapy promotes soluble SR-A1 expression and secretion decreased modified LDL accumulation, foam cell incidence and atherosclerosis [19].

Bottom Line: These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence.Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens.Here, we review our current understanding of SR structure and function implicated in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.

ABSTRACT
Scavenger receptors (SRs) are a 'superfamily' of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.

No MeSH data available.


Related in: MedlinePlus