ApoA-IV modulates the secretory trafficking of apoB and the size of triglyceride-rich lipoproteins

作者：Weinberg Richard B; Gallagher James W; Fabritius Melissa A; Shelness Gregory S^*

来源：The Journal of Lipid Research, 2012, 53(4): 736-743.

DOI：10.1194/jlr.M019992

• lipoprotein assembly
• triglyceride
• lipid trafficking
• very low density lipoprotein
• apolipoprotein B
• apolipoprotein A-IV

Although the evidence linking apoA-IV expression and triglyceride (TG)-rich lipoprotein assembly and secretion is compelling, the intracellular mechanisms by which apoA-IV could modulate these processes remain poorly understood. We therefore examined the functional impact of apoA-IV expression on endogenous apoB, TG, and VLDL secretion in stably transfected McA-RH7777 rat hepatoma cells. Expression of apoA-IV modified with the endoplasmic reticulum (ER) retention signal KDEL (apoA-IV-KDEL) dramatically decreased both the rate and efficiency of endogenous apoB secretion, suggesting a presecretory interaction between apoA-IV-KDEL and apoB or apoB-containing lipoproteins. Expression of native apoA-IV using either a constitutive or tetracycline-inducible promoter delayed the initial rate of apoB secretion and reduced the final secretion efficiency by similar to 40%. However, whereas apoA-IV-KDEL reduced TG secretion by 75%, expression of native apoA-IV caused a 20-35% increase in TG secretion, accompanied by a similar to 55% increase in VLDL-associated apoB, an increase in the TG: phospholipid ratio of secreted d %26lt; 1.006 lipoproteins, and a 10.1 nm increase in peak VLDL1 particle diameter. Native apoA-IV expression had a negligible impact on expression of the MTP gene.(jlr) These data suggest that by interacting with apoB in the secretory pathway, apoA-IV alters the trafficking kinetics of apoB-containing TG-rich lipoproteins through cellular lipidation compartments, which in turn, enhances particle expansion and increases TG secretion.-Weinberg, R. B., J. W. Gallagher, M. A. Fabritius, and G. S. Shelness. ApoA-IV modulates the secretory trafficking of apoB and the size of triglyceride-rich lipoproteins. J. Lipid Res. 2012. 53: 736-743.

• 出版日期2012-4