Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1
The lectin-like oxidized-LDL (oxLDL) receptor LOX-1, which is broadly expressed in vascular cells, represents a key mediator of endothelial activation and dysfunction in atherosclerotic plaque development. Being a member of the C-type lectin receptor family, LOX-1 can bind different ligands, with ox...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2020.594441/full |
| _version_ | 1818944052631961600 |
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| author | Torben Mentrup Florencia Cabrera-Cabrera Bernd Schröder |
| author_facet | Torben Mentrup Florencia Cabrera-Cabrera Bernd Schröder |
| author_sort | Torben Mentrup |
| collection | DOAJ |
| description | The lectin-like oxidized-LDL (oxLDL) receptor LOX-1, which is broadly expressed in vascular cells, represents a key mediator of endothelial activation and dysfunction in atherosclerotic plaque development. Being a member of the C-type lectin receptor family, LOX-1 can bind different ligands, with oxLDL being the best characterized. LOX-1 mediates oxLDL uptake into vascular cells and by this means can promote foam cell formation. In addition, LOX-1 triggers multiple signaling pathways, which ultimately induce a pro-atherogenic and pro-fibrotic transcriptional program. However, the molecular mechanisms underlying this signal transduction remain incompletely understood. In this regard, proteolysis has recently emerged as a regulatory mechanism of LOX-1 function. Different proteolytic cleavages within the LOX-1 protein can initiate its turnover and control the cellular levels of this receptor. Thereby, cleavage products with individual biological functions and/or medical significance are produced. Ectodomain shedding leads to the release of a soluble form of the receptor (sLOX1) which has been suggested to have diagnostic potential as a biomarker. Removal of the ectodomain leaves behind a membrane-bound N-terminal fragment (NTF), which despite being devoid of the ligand-binding domain is actively involved in signal transduction. Degradation of this LOX-1 NTF, which represents an athero-protective mechanism, critically depends on the aspartyl intramembrane proteases Signal peptide peptidase-like 2a and b (SPPL2a/b). Here, we present an overview of the biology of LOX-1 focusing on how proteolytic cleavages directly modulate the function of this receptor and, what kind of pathophysiological implications this has in cardiovascular disease. |
| first_indexed | 2024-12-20T07:37:05Z |
| format | Article |
| id | doaj.art-769934efb31e4e778a3eeb0fe10ed763 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-20T07:37:05Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-769934efb31e4e778a3eeb0fe10ed7632022-12-21T19:48:15ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-01-01710.3389/fcvm.2020.594441594441Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1Torben MentrupFlorencia Cabrera-CabreraBernd SchröderThe lectin-like oxidized-LDL (oxLDL) receptor LOX-1, which is broadly expressed in vascular cells, represents a key mediator of endothelial activation and dysfunction in atherosclerotic plaque development. Being a member of the C-type lectin receptor family, LOX-1 can bind different ligands, with oxLDL being the best characterized. LOX-1 mediates oxLDL uptake into vascular cells and by this means can promote foam cell formation. In addition, LOX-1 triggers multiple signaling pathways, which ultimately induce a pro-atherogenic and pro-fibrotic transcriptional program. However, the molecular mechanisms underlying this signal transduction remain incompletely understood. In this regard, proteolysis has recently emerged as a regulatory mechanism of LOX-1 function. Different proteolytic cleavages within the LOX-1 protein can initiate its turnover and control the cellular levels of this receptor. Thereby, cleavage products with individual biological functions and/or medical significance are produced. Ectodomain shedding leads to the release of a soluble form of the receptor (sLOX1) which has been suggested to have diagnostic potential as a biomarker. Removal of the ectodomain leaves behind a membrane-bound N-terminal fragment (NTF), which despite being devoid of the ligand-binding domain is actively involved in signal transduction. Degradation of this LOX-1 NTF, which represents an athero-protective mechanism, critically depends on the aspartyl intramembrane proteases Signal peptide peptidase-like 2a and b (SPPL2a/b). Here, we present an overview of the biology of LOX-1 focusing on how proteolytic cleavages directly modulate the function of this receptor and, what kind of pathophysiological implications this has in cardiovascular disease.https://www.frontiersin.org/articles/10.3389/fcvm.2020.594441/fullLOX-1atherosclerosisproteaseintramembrane proteaseectodomain sheddingsignal transduction |
| spellingShingle | Torben Mentrup Florencia Cabrera-Cabrera Bernd Schröder Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1 Frontiers in Cardiovascular Medicine LOX-1 atherosclerosis protease intramembrane protease ectodomain shedding signal transduction |
| title | Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1 |
| title_full | Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1 |
| title_fullStr | Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1 |
| title_full_unstemmed | Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1 |
| title_short | Proteolytic Regulation of the Lectin-Like Oxidized Lipoprotein Receptor LOX-1 |
| title_sort | proteolytic regulation of the lectin like oxidized lipoprotein receptor lox 1 |
| topic | LOX-1 atherosclerosis protease intramembrane protease ectodomain shedding signal transduction |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2020.594441/full |
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