Abstract
The cellular mechanisms and pathways by which lipoprotein lipase (LPL) enhances the binding and uptake of lipoproteins remains unknown. Confocal and immunoelectron microscopy demonstrated that primary binding of bovine LPL (bLPL) occurs at the microvilli surface of HepG2 cells and hepatocytes. Internalized bLPL was associated with endocytic vesicles and multivesicular bodies. Quantitative immunofluorescence indicated that the presence of bLPL caused a marked increase in the cell-surface binding of DiI-conjugated triacylglycerol-rich lipoproteins (DiI-TRL). Confocal microscopy showed that when DiI-TRL was incubated with bLPL at 4°C, the distributions of bound LPL and DiI-TRL were totally coincident, and covered the apical surface of both HepG2 cells and hepatocytes. When incubated separately, the time-courses of the internalization of fluorescence associated with DiI-TRL and bLPL were different: DiI-TRL was quickly internalized by both HepG2 cells and hepatocytes, and reached a plateau at 30 min, whereas intracellular LPL increased continuously, but more slowly in the same period. In the presence of bLPL, DiI-TRL was internalized progressively by HepG2 and by cultured hepatocytes for up to 1 h and no saturation was reached. At this time the intensity of labeling of bLPL was lower than of DiI-TRL and a higher number of DiI spots did not colocalize with bLPL immunofluorescence, suggesting that the ligands follow a different pathway after internalization. The data suggest that when lipoprotein lipase (LPL) is associated with the lipoproteins it directs them to specific endocytic pathways. A hypothetical model of the intracellular pathways followed by triacylglycerol-rich lipoproteins and LPL after internalization is proposed.—Casaroli-Marano, R. P., R. García, E. Vilella, G. Olivecrona, M. Reina, and S. Vilaró. Binding and intracellular trafficking of lipoprotein lipase and triacylglycerol-rich lipoproteins by liver cells. J. Lipid Res. 1998. 39: 789–806.
Highlights
The cellular mechanisms and pathways by which lipoprotein lipase (LPL) enhances the binding and uptake of lipoproteins remains unknown
Fatty acids are delivered to the peripheral tissues by two types of triacylglycerol-rich lipoproteins (TRL): chylomicrons, which are synthesized in the intestine and transport dietary lipids to various tissues, and very low density lipoproteins (VLDL), which are synthesized in the liver and transport endogenous lipids
HepG2 cells were incubated with bovine LPL (bLPL) at 4ЊC for 30 min and immunofluorescence was analyzed by confocal microscopy (Fig. 1)
Summary
The cellular mechanisms and pathways by which lipoprotein lipase (LPL) enhances the binding and uptake of lipoproteins remains unknown. Quantitative immunofluorescence indicated that the presence of bLPL caused a marked increase in the cell-surface binding of DiI-conjugated triacylglycerol-rich lipoproteins (DiI-TRL). Fatty acids are delivered to the peripheral tissues by two types of triacylglycerol-rich lipoproteins (TRL): chylomicrons, which are synthesized in the intestine and transport dietary lipids to various tissues, and very low density lipoproteins (VLDL), which are synthesized in the liver and transport endogenous lipids In the circulation they undergo diverse modifications such as acquisition of apolipoproteins from other circulating lipoproteins and hydrolysis of their triacylglycerides, catalyzed by lipoprotein lipase (LPL; EC 3.1.1.34) (see 1, 2 for recent reviews). The resulting lipoproteins, known as remnant particles, are smaller and denser, and have altered lipid and apolipoprotein composition These new particles are quickly catabolized by the liver. The cellular mechanisms of LPL binding and uptake seem to be rather complex and the function and physiological relevance are not fully understood
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