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Journal of Lipid Research, Vol. 43, 1496-1507, September 2002
Copyright © 2002 by Lipid Research, Inc.

The N-linked oligosaccharides at the amino terminus of human apoB are important for the assembly and secretion of VLDL

Jelena Vukmirica^*, Tomoko Nishimaki-Mogami, Khai Tran^*, Jing Shan^*, Roger S. McLeod^1,*, Jane Yuan^* and Zemin Yao^2,*

^* Lipoprotein and Atherosclerosis Group, Departments of Pathology and Laboratory Medicine and Biochemistry, Microbiology, and Immunology, University of Ottawa Heart Institute, Ottawa, ON, Canada, K1Y 4W7
National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan

² To whom correspondence should be addressed. e-mail: zyao{at}ottawaheart.ca

We determined the role of N-linked glycosylation of apolipoprotein B (apoB) in the assembly and secretion of lipoproteins using transfected rat hepatoma McA-RH7777 cells expressing human apoB-17, apoB-37, and apoB-50, three apoB variants with different ability to recruit neutral lipids. Substituting Asn residue with Gln at the single glycosylation site within apoB-17 (N¹⁵⁸) decreased its secretion efficiency to a level equivalent to that of wild-type apoB-17 treated with tunicamycin, but had little effect on its synthesis or intracellular distribution. When selective N-to-Q substitution was introduced at one or more of the five N-linked glycosylation sites within apoB-37 (N¹⁵⁸, N⁹⁵⁶, N¹³⁴¹, N¹³⁵⁰, and N¹⁴⁹⁶), secretion efficiency of apoB-37 from transiently transfected cells was variably affected. When all five N-linked glycosylation sites were mutated within apoB-37, the secretion efficiency and association with lipoproteins were decreased by >50% as compared with wild-type apoB-37. Similarly, mutant apoB-50 with all of its N-linked glycosylation sites mutagenized showed decreased secretion efficiency and decreased lipoprotein association in both d < 1.02 and d > 1.02 g/ml fractions. The inability of mutant apoB-37 and apoB-50 to associate with very low-density lipoproteins was attributable to impaired assembly and was not due to the limitation of lipid availability. The decreased secretion of mutant apoB-17 and apoB-37 was not accompanied by accumulation within the cells, suggesting that the proportion of mutant apoB not secreted was rapidly degraded. However unlike apoB-17 or apoB-37, accumulation of mutant apoB-50 was observed within the endoplasmic reticulum and Golgi compartments.

These data imply that the N-glycans at the amino terminus of apoB play an important role in the assembly and secretion of lipoproteins containing the carboxyl terminally truncated apoB.

Abbreviations: apo, apolipoprotein; ER, endoplasmic reticulum; GFP, green fluorescent protein; MTP, microsomal triglyceride transfer protein; TG, triacylglycerol

Supplementary key words apoB-17 • apoB-37 • apoB-50 • McA-RH7777 cell • subcellular fractionation

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