Apolipoprotein B48 glycosylation in abetalipoproteinemia and Anderson's disease.
OBJECTIVE
Abetalipoproteinemia and Anderson's disease are hereditary lipid malabsorption syndromes. In abetalipoproteinemia, lipoprotein assembly is defective because of mutations in the microsomal triglyceride transfer protein. Here, we evaluated the intracellular transport of apolipoprotein B48 to localize the defect in Anderson's disease.


METHODS
Asparagine-linked oligosaccharide processing of apolipoprotein B48 in normal and affected individuals was determined by the endoglycosidase H and F sensitivities of the protein after metabolic labeling of intestinal explants in organ culture. 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 oligosaccharides, added in the Golgi network. In contrast, despite the translocation of apolipoprotein B48 into the endoplasmic reticulum in patients with abetalipoproteinemia and in biopsies treated with Brefeldin A, which blocks anterograde transport between the endoplasmic reticulum and the Golgi network, there was no transformation of endoglycosidase H-sensitive oligosaccharides.


CONCLUSIONS
In abetalipoproteinemia and Anderson's disease, apolipoprotein B48 is completely translocated into the endoplasmic reticulum, but only in Anderson's disease is the protein transported to the Golgi apparatus. This suggests that Anderson's disease is caused by a post-Golgi cargo-specific secretion defect.
Berriot-Varoqueaux
N
N
U327 Institut National de la Santé et de la Recherche Médicale, Paris, France.
Dannoura
A H
AH
Moreau
A
A
Verthier
N
N
Sassolas
A
A
Cadiot
G
G
Lachaux
A
A
Munck
A
A
Schmitz
J
J
Aggerbeck
L P
LP
Samson-Bouma
M E
ME
D000012:Abetalipoproteinemia / Q000378:metabolism* / Q000473:pathology; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000172:deficiency / Q000378:metabolism*; D001692:Biological Transport; D020126:Brefeldin A / Q000627:therapeutic use; D002352:Carrier Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D050356:Lipid Metabolism
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein; D020126:Brefeldin A