The splice variant LOXIN inhibits LOX-1 receptor function through hetero-oligomerization

Journal of Molecular and Cellular Cardiology
Silvia BioccaGiuseppe Novelli

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, is a scavenger receptor that plays a central role in the pathogenesis of atherosclerosis. We have recently identified a truncated naturally occurring variant of the human receptor LOX-1, named LOXIN, which lacks part of the C-terminus lectin-like domain. In vivo and in vitro studies support that the new splicing isoform is protective against acute myocardial infarction. The mechanism by which LOXIN exerts its protective role is unknown. In this paper we report studies on the heterologous expression and functional characterization of LOXIN variant in mammalian fibroblasts and human endothelial cells. We found that LOXIN, when expressed in the absence of LOX-1, shows diminished plasma membrane localization and is deficient in ox-LDL ligand binding. When co-transfected with the full-length counterpart LOX-1, the two isoforms interact to form LOX-1 oligomers and their interaction leads to a decrease in the appearance of LOX-1 receptors in the plasma membrane and a marked impairment of ox-LDL binding and uptake. Co-immunoprecipitation studies confirmed the molecular LOX-1/LOXIN interaction and the formation of non-functional hetero-oligomers. ...Continue Reading

References

Sep 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·X M YuanA G Olsson
Feb 15, 2000·European Journal of Biochemistry·M LenerS Biocca
Nov 2, 2002·Nature Medicine·Christoph J BinderJoseph L Witztum
Dec 19, 2003·Protein Expression and Purification·Qiuhong XieSachiko Machida
Oct 30, 2004·The Journal of Biological Chemistry·Alessio CardinaleSilvia Biocca
Dec 14, 2004·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Julian C Knight
Feb 8, 2005·The Journal of Biological Chemistry·HaJeung ParkJeffrey C Boyington
Mar 8, 2005·Trends in Pharmacological Sciences·Sébastien BulengerMichel Bouvier
Feb 14, 2006·Trends in Cardiovascular Medicine·Ravinder S VohraShervanthi Homer-Vanniasinkam
May 5, 2007·Circulation Research·Jawahar L MehtaTatsuya Sawamura

❮ Previous
Next ❯

Citations

Aug 12, 2014·BioMed Research International·Felipe A ZunigaClaudio Aguayo
Oct 29, 2010·International Journal of Hypertension·Sam L StephenSreenivasan Ponnambalam
Dec 17, 2009·Journal of Atherosclerosis and Thrombosis·Teresa NavarraGiuseppina Basta
Aug 2, 2011·Cardiovascular Drugs and Therapy·Ryo YoshimotoTatsuya Sawamura
Apr 26, 2013·Circulation. Cardiovascular Genetics·Irene M PredazziScott M Williams
May 3, 2012·TheScientificWorldJournal·Susanne SattlerErhard Hofer
Aug 19, 2011·Cardiovascular Drugs and Therapy·Jingjun Lü, Jawahar L Mehta
Sep 10, 2011·Cardiovascular Drugs and Therapy·Ruggiero MangoGiuseppe Novelli
May 23, 2014·FEBS Letters·Deenadayalan BakthavatsalamDarren G Woodside
Feb 26, 2016·Microvascular Research·Valter Lubrano, Silvana Balzan
Nov 7, 2015·Journal of Cellular and Molecular Medicine·Elena MoriniFrancesca Amati
Aug 23, 2012·Gene·Olga KelemenStefan Stamm
Aug 19, 2015·Journal of Molecular Biology·Frédérick BouffardFrancine Durocher
Apr 19, 2013·European Journal of Clinical Investigation·Ashraf Taye, Azza A K El-Sheikh
May 8, 2015·Cell Cycle·Silvia BioccaMattia Falconi
Aug 13, 2013·Mediators of Inflammation·Angela PirilloAlberico Luigi Catapano
Jul 31, 2013·Biochemical and Biophysical Research Communications·Mattia FalconiSilvia Biocca
Oct 15, 2010·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Stephen J WhiteAndrew C Newby
Oct 12, 2013·Archives of Biochemistry and Biophysics·Silvia BioccaMattia Falconi
Sep 14, 2014·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Daniel James ShawRamzi Ajjan
Oct 27, 2015·PloS One·Magda GioiaSilvia Biocca
Feb 2, 2017·International Journal of Molecular Sciences·Barbara RizzacasaFrancesca Amati
Apr 15, 2017·Genetic Testing and Molecular Biomarkers·Valentina BrunoFrancesca Amati
Jun 3, 2017·Journal of the American College of Cardiology·Naga Venkata K PothineniJawahar L Mehta
May 10, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mercy R PrabhuDasJoseph El Khoury
Nov 26, 2009·Genetic Testing and Molecular Biomarkers·Maria Teresa VietriMichele Cioffi
Jul 9, 2008·Current Opinion in Lipidology·Marco Baralle, Francisco E Baralle
May 9, 2018·Current Medicinal Chemistry·Ajoe John KattoorJawahar L Mehta
Aug 13, 2013·Molecular and Cellular Biochemistry·Valter Lubrano, Silvana Balzan
Feb 25, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mercy PrabhudasJoseph El Khoury
Feb 2, 2021·Heart & Lung : the Journal of Critical Care·Pouya SalehipourMohammad Hossein Modarressi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.