News on the molecular regulation and function of hepatic low-density lipoprotein receptor and LDLR-related protein 1

Bart Van De Sluis, Melinde Wijers, Joachim Herz

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Purpose of review Clearing of atherogenic lipoprotein particles by the liver requires hepatic low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1). This review highlights recent studies that have expanded our understanding of the molecular regulation and metabolic functions of LDLR and LRP1 in the liver. Recent findings Various proteins orchestrate the intracellular trafficking of LDLR and LRP1. After internalization, the receptors are redirected via recycling endosomes to the cell surface. Several new endocytic proteins that facilitate the endosomal trafficking of LDLR and consequently the clearance of circulating LDL cholesterol have recently been reported. Mutations in some of these proteins cause hypercholesterolemia in human. In addition, LRP1 controls cellular cholesterol efflux by modulating the expression of ABCA1 and ABCG1, and hepatic LRP1 protects against diet-induced hepatic insulin resistance and steatosis through the regulation of insulin receptor trafficking. Summary LDLR and LRP1 have prominent roles in cellular and organismal cholesterol homeostasis. Their functioning, including their trafficking in the cell, is controlled by numerous proteins. Comprehensive studies into the molecular regulation of LDLR and LRP1 trafficking have advanced our fundamental understanding of cholesterol homeostasis, and these insights may lead to novel therapeutic strategies for atherosclerosis, hyperlipidemia and insulin resistance in the future.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalCurrent Opinion in Lipidology
Volume28
Issue number3
DOIs
StatePublished - Jun 1 2017

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Low Density Lipoprotein Receptor-Related Protein-1
LDL Receptors
Liver
Proteins
Cholesterol
Insulin Resistance
Homeostasis
Endosomes
Insulin Receptor
Protein Transport
Hypercholesterolemia
Hyperlipidemias
LDL Cholesterol
Lipoproteins
Atherosclerosis
Diet
Mutation

Keywords

  • CCC complex
  • disabled homolog 2
  • glucose metabolism
  • hypercholesterolemia
  • trafficking

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Genetics
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

News on the molecular regulation and function of hepatic low-density lipoprotein receptor and LDLR-related protein 1. / Van De Sluis, Bart; Wijers, Melinde; Herz, Joachim.

In: Current Opinion in Lipidology, Vol. 28, No. 3, 01.06.2017, p. 241-247.

Research output: Contribution to journalReview article

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