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Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2

Murphy, JE; Vohra, RS; Dunn, S; Holloway, ZG; Monaco, AP; Homer-Vanniasinkam, S; ... Ponnambalam, S; + view all (2008) Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. J CELL SCI , 121 (13) 2136 - 2147. 10.1242/jcs.020917.

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Abstract

The LOX-1 scavenger receptor recognises pro-atherogenic oxidised low-density lipoprotein (OxLDL) particles and is implicated in atherosclerotic plaque formation, but this mechanism is not well understood. Here we show evidence for a novel clathrin-independent and cytosolic-signal-dependent pathway that regulates LOX-1-mediated OxLDL internalisation. Cell surface labelling in the absence or presence of OxLDL ligand showed that LOX-1 is constitutively internalised from the plasma membrane and its half-life is not altered upon ligand binding and trafficking. We show that LOX-1-mediated OxLDL uptake is disrupted by overexpression of dominant-negative dynamin-2 but unaffected by CHC17 or mu 2 (AP2) depletion. Site-directed mutagenesis revealed a conserved and novel cytoplasmic tripeptide motif (DDL) that regulates LOX-1-mediated endocytosis of OxLDL. Taken together, these findings indicate that LOX-1 is internalised by a clathrin-independent and dynamin-2-dependent pathway and is thus likely to mediate OxLDL trafficking in vascular tissues.

Type:Article
Title:Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2
DOI:10.1242/jcs.020917
Keywords:LOX-1, OxLDL, endocytosis, dynamin-2, LOW-DENSITY-LIPOPROTEIN, CLATHRIN-INDEPENDENT ENDOCYTOSIS, COATED VESICLE FORMATION, FOAM CELL-FORMATION, LECTIN-LIKE DOMAIN, MEDIATED ENDOCYTOSIS, ENDOTHELIAL-CELLS, ATHEROSCLEROTIC LESIONS, MYOCARDIAL-INFARCTION, PIT FORMATION
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)

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