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

Jane E Murphy, Ravinder S Vohra, Sarah Dunn, Zoe G Holloway, Anthony P Monaco, Shervanthi Homer-Vanniasinkam, John H Walker, Sreenivasan Ponnambalam

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

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 mu2 (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.
Original languageEnglish
Pages (from-to)2136-47
Number of pages12
JournalJournal of Cell Science
Volume121
Issue numberPt 13
DOIs
Publication statusPublished - 1 Jul 2008

Keywords

  • HeLa Cells
  • Humans
  • Amino Acid Sequence
  • Dynamin II
  • Protein Binding
  • Mutagenesis, Site-Directed
  • Endocytosis
  • Amino Acid Motifs
  • Scavenger Receptors, Class E
  • Molecular Sequence Data
  • Lipoproteins, LDL
  • Protein Structure, Tertiary
  • Signal Transduction
  • Protein Transport

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