Apolipoprotein B48 glycosylation in abetalipoproteinemia and Anderson's disease

Background & Aims: Abetalipoproteinemia and Anderson's disease are heredita ry lipid malabsorption syndromes. In abetalipoproteinemia, lipoprotein asse mbly is defective because of mutations in the microsomal triglyceride trans fer protein. Here, we evaluated the intracellular transport of apolipoprote in B48 to localize the defect in Anderson's disease. Methods: Asparagine-li nked oligosaccharide processing of apolipoprotein B48 in normal and affecte d individuals was determined by the endoglycosidase H and IF sensitivities of the protein after metabolic labeling of intestinal explants in organ cul ture. Cell ultrastructure was evaluated with electron microscopy. Results: In Anderson's disease as in normal individuals, there was a time-dependent transformation of high mannose endoglycosidase H-sensitive oligosaccharides , of endoplasmic reticulum origin, to complex endoglycosidase H-resistant o ligosaccharides, added in the Golgi network. In contrast, despite the trans location of apolipoprotein B48 into the endoplasmic reticulum in patients w ith abetalipoproteinemia and in biopsies treated with Brefeldin A, which bl ocks anterograde transport between the endoplasmic reticulum and the Golgi network, there was no transformation of endoglycosidase H-sensitive oligosa ccharides. Conclusions: In abetalipoproteinemia and Anderson's disease, apo lipoprotein B48 is completely translocated into the endoplasmic reticulum, but only in Anderson's disease is the protein transported to the Golgi appa ratus. This suggests that Anderson's disease is caused by a post-Golgi carg o-specific secretion defect.