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Journal of Lipid Research, Vol. 46, 104-114, January 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Relation of the size and intracellular sorting of apoB to the formation of VLDL 1 and VLDL 2

Pia Stillemark-Billton¹, Caroline Beck¹, Jan Borén and Sven-Olof Olofsson²

Department of Medical Biochemistry and the Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Göteborg, Sweden

² To whom correspondence should be addressed. e-mail: sven-olof.olofsson{at}wlab.gu.se

In this study, we tested the hypothesis that two separate pathways, the two-step process and an apolipoprotein B (apoB) size-dependent lipidation process, give rise to different lipoproteins. Expression of apoB-100 and C-terminally truncated forms of apoB-100 in McA-RH7777 cells demonstrated that VLDL particles can be assembled by apoB size-dependent linear lipidation, resulting in particles whose density is inversely related to the size of apoB. This lipidation results in a LDL-VLDL 2 particle containing apoB-100. VLDL 1 is assembled by the two-step process by apoB-48 and larger forms of apoB but not to any significant amount by apoB-41. The major amount of intracellular apoB-80 and apoB-100 banded with a mean density of 1.10 g/ml. Its formation was dependent on the sequence between apoB-72 and apoB-90. This dense particle, which is retained in the cell, possibly by chaperones or association with the microsomal membrane, is a precursor of secreted VLDL 1. The intracellular LDL-VLDL 2 particles formed during size-dependent lipidation appear to be the precursors of intracellular VLDL 1.

We propose that the dense apoB-100 intracellular particle is converted to LDL-VLDL 2 by size-dependent lipidation. LDL-VLDL 2 is secreted or converted to VLDL 1 by the uptake of the major amount of triglycerides.

Abbreviations: apoB, apolipoprotein B; BiP, binding protein; GRP94, glucose regulatory protein 94; LDLR, low density lipoprotein receptor; MTP, microsomal triglyceride transfer protein; PDI, protein disulfide isomerase

Supplementary key words chaperones • microsomal triglyceride transfer protein • intracellular retention • apolipoprotein B • very low density lipoprotein

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