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 language | English |
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Pages (from-to) | 2136-47 |
Number of pages | 12 |
Journal | Journal of Cell Science |
Volume | 121 |
Issue number | Pt 13 |
DOIs | |
Publication status | Published - 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