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First published online 10 June 2008
doi: 10.1242/jcs.020917

Journal of Cell Science 121, 2136-2147 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Jane E. Murphy1, Ravinder S. Vohra1, Sarah Dunn1, Zoe G. Holloway2, Anthony P. Monaco2, Shervanthi Homer-Vanniasinkam1, John H. Walker1 and Sreenivasan Ponnambalam1,*

1 Endothelial Cell Biology Unit, Leeds Institute of Genetics, Health & Therapeutics, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK
2 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, UK

* Author for correspondence (e-mail: s.ponnambalam{at}leeds.ac.uk)

Accepted 9 April 2008

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 µ2 (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.

Key words: LOX-1, OxLDL, Endocytosis, Dynamin-2


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