title: Regulation of the assembly and secretion of very low density lipoproteins by the liver.
abstract: Recent studies have suggested that there are three sites at which VLDL secretion by the liver may be controlled: (i) Newly synthesised apo-B either remains associated with the RER membrane and is degraded by the ubiquitin/proteasome system, or is translocated into the lumen and incorporated into lipid poor VLDL precursors; (ii) the lumenal apo-B is either degraded or moves on, and (iii) acquires the remaining VLDL lipids in the SER/cis-Golgi. Newly synthesised apo-B, at the cytosolic side of the RER, is stabilised and protected from degradation by the chaperone protein, hsp-70. Triacylglycerol, cholesterol ester and phospholipids have all been implicated in the translocation of apo-B and microsomal triglyceride protein plays a major role. If translocation does not occur then the apo-B is degraded. Dietary fish-oils, but not sunflower oil, inhibit movement of apo-B containing precursors from the RER and their assembly with lipids and target lumenal apo-B to degradation. This effect is reversed by inhibition of lumenal proteolysis, but not by inhibition of cytosolic proteolysis. Therefore lumenal degradation of apo-B and secretion appear to be in balance, so that if assembly of VLDL precursors is slowed, then degradation becomes predominant. If however, degradation is inhibited then VLDL assembly can proceed. These observations suggest that movement of VLDL precursors from the RER lumen to the second stage of assembly may be a further regulated step.
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Kendrick
authors.forename: J
authors.initials: J
authors.lastname: Wilkinson
authors.forename: I J
authors.initials: IJ
authors.lastname: Cartwright
authors.forename: S
authors.initials: S
authors.lastname: Lawrence
authors.forename: J A
authors.initials: JA
authors.lastname: Higgins
mesh_terms: D000818:Animals; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D008079:Lipoproteins, VLDL