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The amino terminus of apolipoprotein B is necessary but not sufficient for Microsomal triglyceride transfer protein responsiveness

Gretch, DG; Sturley, SL; Wang, L; Lipton, BA; Dunning, A; Grunwald, KAA; ... Attie, AD; + view all (1996) The amino terminus of apolipoprotein B is necessary but not sufficient for Microsomal triglyceride transfer protein responsiveness. J BIOL CHEM , 271 (15) 8682 - 8691. Gold open access

Abstract

Human apolipoprotein (apo) B mediates the formation of neutral Lipid-containing lipoproteins in the liver and intestine. The association of apoB with lipid is thought to be promoted by the microsomal triglyceride transfer protein complex. We have reconstituted lipoprotein assembly in an insect cell line that normally does not support this process. Expression of human microsomal triglyceride transfer protein (MTP) and apolipoprotein B48 (apoB48) together enabled Sf-21 insect cells to secrete similar to 60-fold more lipoprotein-associated triacylglycerol than control cells. This dramatic effect demonstrates that effective partitioning of triacylglycerol into the secretory pathway requires an endoplasmic reticulum-associated neutral lipid transporter (provided by MTP) and an apolipoprotein to shuttle the lipid through the pathway. Expression of the human apoB48 gene in insect cells resulted in secretion of the protein product, Including both MTP subunits with apoB48 and oleic acid specifically increased apoB48 secretion 8-fold over individual subunits alone. To assess whether specific regions of apoB are necessary for MTP responsiveness, nine apoB segments were expressed. These included NH2-terminal segments as well as internal and COOH-terminal regions of apoB fused with a heterologous signal sequence, ApoB segments containing the NH2-terminal 17% of the protein mere secreted and responded to NTP activity; however, a segment containing only the NH2-terminal 17% of the protein was not significantly responsive to MTP. Segments lacking the NH2 terminus were not MTP-responsive, and five of six of these proteins were trapped intracellularly but, in certain cases, could be rescued by fusion to apoB17. These results suggest that the NH2 terminus of apoB is necessary but not sufficient for MTP responsiveness.

Type:Article
Title:The amino terminus of apolipoprotein B is necessary but not sufficient for Microsomal triglyceride transfer protein responsiveness
Open access status:An open access publication
Publisher version:http://www.jbc.org/content/early/recent/0
Keywords:LOW-DENSITY LIPOPROTEINS, LIPID TRANSFER PARTICLE, HEP G2 CELLS, ENDOPLASMIC-RETICULUM, MONOCLONAL-ANTIBODIES, PHOSPHOLIPID-BILAYERS, TRANSLOCATION, SECRETION, SEQUENCE, B-100
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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