Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2.
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 t...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1797056366221721600 |
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| author | Murphy, J Vohra, R Dunn, S Holloway, Z Monaco, A Homer-Vanniasinkam, S Walker, J Ponnambalam, S |
| author_facet | Murphy, J Vohra, R Dunn, S Holloway, Z Monaco, A Homer-Vanniasinkam, S Walker, J Ponnambalam, S |
| author_sort | Murphy, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:22:24Z |
| format | Journal article |
| id | oxford-uuid:1a8d70da-a245-4a74-973e-8198bfa4da77 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:22:24Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:1a8d70da-a245-4a74-973e-8198bfa4da772022-03-26T10:55:29ZOxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1a8d70da-a245-4a74-973e-8198bfa4da77EnglishSymplectic Elements at Oxford2008Murphy, JVohra, RDunn, SHolloway, ZMonaco, AHomer-Vanniasinkam, SWalker, JPonnambalam, SThe 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. |
| spellingShingle | Murphy, J Vohra, R Dunn, S Holloway, Z Monaco, A Homer-Vanniasinkam, S Walker, J Ponnambalam, S Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. |
| title | Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. |
| title_full | Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. |
| title_fullStr | Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. |
| title_full_unstemmed | Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. |
| title_short | Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2. |
| title_sort | oxidised ldl internalisation by the lox 1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin 2 |
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