title: The molecular mechanism for the assembly and secretion of ApoB-100-containing lipoproteins.
abstract: We have reviewed the literature on the intracellular transport of ApoB-100 and the assembly of the ApoB-100-containing lipoproteins. ApoB-100 is a large molecule (4536 aa) that requires some 15 min to be completed. During the synthesis, the protein could take one of two pathways: a degradational pathway and a pathway that leads to secretion of the protein on mature lipoproteins. The degradational pathway starts with a cotranslational incorporation of ApoB-100 into the membrane of the endoplasmic reticulum in such a way that a relatively large portion of the sequence is exposed on the cytoplasmic surface of this membrane. The membrane bound ApoB-100 is retained in the ER and will eventually undergo intracellular degradation. To enter the pathway that leads to lipoprotein formation, ApoB-100 has to be cotranslationally translocated to the lumen of the ER. ApoB-100 will interact with the lipids during this translation-translocation process and the mature lipoprotein is released into the lumen of the secretory pathway when ApoB-100 is completed and leaves the ribosome. In addition to the mature lipoproteins, the secretory pathway contains an ApoB-100-containing lipoprotein with the density of a HDL particle. This particle is not secreted from the cells but is retained and eventually degraded. Of importance for the retention are sequences present in the C-terminal half of the protein. The mature lipoproteins rapidly leave the ER lumen and are transported to the Golgi apparatus, through which transfer takes considerably longer. The assembly process is a potential site for the regulation of the secretion of the ApoB-100-containing lipoproteins. This process is dependent on active synthesis of phosphatidylcholine and it is also highly dependent on the rate of triacylglycerol synthesis. On the other hand, ApoB-100 appears to be constitutively expressed. An increase in the rate of lipoprotein assembly induced by an increased triacylglycerol synthesis gives rise to an increased recruitment of ApoB-100 nascent polypeptides to interact cotranslationally with lipids. ApoB-100 that is not used for lipoprotein assembly is cotranslationally bound to the ER membrane and sorted to degradation.
authors.affiliation: Department of Medical Biochemistry, University of Göteborg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Borén
authors.forename: A
authors.initials: A
authors.lastname: White
authors.forename: M
authors.initials: M
authors.lastname: Wettesten
authors.forename: J
authors.initials: J
authors.lastname: Scott
authors.forename: L
authors.initials: L
authors.lastname: Graham
authors.forename: S O
authors.initials: SO
authors.lastname: Olofsson
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D051381:Rats
chemical_list: D001055:Apolipoproteins B; D008055:Lipids