title: News on the molecular regulation and function of hepatic low-density lipoprotein receptor and LDLR-related protein 1.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aSection of Molecular Genetics, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands bDepartments of Molecular Genetics, Neuroscience, Neurology and Neurotherapeutics, Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: van de Sluis
authors.forename: Melinde
authors.initials: M
authors.lastname: Wijers
authors.forename: Joachim
authors.initials: J
authors.lastname: Herz
mesh_terms: D000818:Animals; D006801:Humans; D008099:Liver / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*
chemical_list: D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011973:Receptors, LDL