Endocytosis of Hepatic Lipase and Lipoprotein Lipase into Rat Liver Hepatocytes in Vivo Is Mediated by the Low Density Lipoprotein Receptor-related Protein

• Published in: The Journal of biological chemistry Vol. 279; no. 10; pp. 9030 - 9036
• Main Authors: Vergés, Marcel, Bensadoun, Andre, Herz, Joachim, Belcher, John D., Havel, Richard J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05-03-2004; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Endocytosis; Hepatocytes - metabolism; Lipase - metabolism; Lipoprotein Lipase - metabolism; Liver - metabolism; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; Male; Rats; Rats, Sprague-Dawley; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M312908200

In isolated cell studies, the internalization and degradation of hepatic lipase (HL) has been linked to its binding to the low density lipoprotein receptor-related protein (LRP). We have utilized the receptor-associated protein (RAP), a universal inhibitor of high affinity ligand binding to LRP, to evaluate the participation of LRP in the endocytosis of HL and lipoprotein lipase (LPL). We isolated a total endosome fraction from rat livers after a 30-min infusion of recombinant RAP, administered as a glutathione S-transferase conjugate (GST-RAP). GST-RAP infusion had no effect on the concentration of HL in liver homogenates, but its concentration in blood plasma increased progressively by 20%, and enrichment over homogenate of HL in endosomes was reduced by 50% as compared with infusion of GST alone. The concentrations of LPL in liver and plasma were 1.4 and 0.5%, respectively, those of HL, but endosomal enrichment of the two enzymes was similar (∼10-fold). GST-RAP infusion had no effect on the concentration of LPL in liver but increased its concentration in blood plasma by 250% and reduced its endosomal enrichment by 95% or greater. GST-RAP infusion also reduced endosomal enrichment of LRP by 40%, but enrichment of several other endocytic receptors was unaffected. Endosomal enrichment of several membrane trafficking proteins associated with the endocytic pathway in hepatocytes was unaffected by GST-RAP with the exception of early endosome endosome antigen 1, which was reduced by 85%. We conclude that HL is partially and LPL almost exclusively taken up into rat hepatocytes after binding to the endocytic receptor LRP.