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The life cycle of the low-density lipoprotein receptor: insights from cellular and in-vivo studies

Wijers, Melinde; Kuivenhoven, Jan A.; van de Sluis, Bart

Current Opinion in Lipidology: April 2015 - Volume 26 - Issue 2 - p 82–87
doi: 10.1097/MOL.0000000000000157
GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele
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Purpose of review Long-term exposure to elevated concentrations of LDL cholesterol increases the risk of cardiovascular events. The main player in clearing LDL cholesterol is the LDL receptor (LDLR) trafficking pathway; however, our fundamental knowledge about the mechanisms regulating this pathway is still incomplete.

Recent findings The LDLR pathway is very complex and involves multiple proteins. Endocytosis is regulated by two different adaptor proteins, that is, autosomal recessive hypercholesterolemia and Disabled-2. The proteolysis of the LDLR is regulated by inducible degrader of the LDLR and proprotein convertase subtilisin/kexin type 9. However, only a few proteins have been identified that provide insights into the endosomal sorting and recycling of the LDLR.

Summary Since the discovery of LDLR, knowledge about its function has greatly expanded. As a result of its importance in maintaining homeostatic LDL levels, the LDLR pathway has emerged as a key therapeutic target to reduce circulating cholesterol. In order to be able to treat and diagnose individuals with hypercholesterolemia in the future, it is important to learn more about the LDLR trafficking pathway, as we still lack a full mechanistic understanding of how LDLR trafficking is controlled.

Molecular Genetics Section, Department of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands

Correspondence to Bart van de Sluis, Molecular Genetics Section, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands. E-mail: a.j.a.van.de.sluis@umcg.nl

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