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J. Biol. Chem., Vol. 277, Issue 35, 31516-31525, August 30, 2002
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From the Canadian Institutes for Health Research Group in Molecular
and Cell Biology of Lipids, and the Department of Medicine, University
of Alberta, Edmonton, Alberta T6G 2S2, Canada
The assembly of very low density
lipoproteins in hepatocytes requires the microsomal
triacylglycerol transfer protein (MTP). This microsomal lumenal protein
transfers lipids, particularly triacylglycerols (TG), between membranes
in vitro and has been proposed to transfer TG to nascent
apolipoprotein (apo) B in vivo. We examined the role of MTP
in the assembly of apoB-containing lipoproteins in cultured murine
primary hepatocytes using an inhibitor of MTP. The MTP inhibitor
reduced TG secretion from hepatocytes by 85% and decreased the amount
of apoB100 in the microsomal lumen, as well as that secreted into the
medium, by 70 and 90%, respectively, whereas the secretion of apoB48
was only slightly decreased and the amount of lumenal apoB48 was
unaffected. However, apoB48-containing particles formed in the presence
of inhibitor were lipid-poor compared with those produced in the
absence of inhibitor. We also isolated a pool of apoB-free TG from the
microsomal lumen and showed that inhibition of MTP decreased the amount
of TG in this pool by ~45%. The pool of TG associated with apoB was
similarly reduced. However, inhibition of MTP did not directly block TG transfer from the apoB-independent TG pool to partially lipidated apoB
in the microsomal lumen. We conclude that MTP is required for TG
accumulation in the microsomal lumen and as a source of TG for assembly
with apoB, but normal levels of MTP are not required for transferring
the bulk of TG to apoB during VLDL assembly in murine hepatocytes.
Microsomal Triacylglycerol Transfer Protein Is Required for
Lumenal Accretion of Triacylglycerol Not Associated with ApoB, as
Well as for ApoB Lipidation*
*
This work was supported by an operating grant from the Heart
and Stroke Foundation of Alberta, Northwest Territories, and Nunavut.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: 332 Heritage Medical
Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2,
Canada. Tel.: 780-492-7250; Fax: 780-492-3383 E-mail: jean.vance@ualberta.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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