Published online before print December 23, 2004, doi: 10.1161/01.ATV.0000154135.21689.47
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© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Role of ADP Ribosylation Factor 1 in the Assembly and Secretion of ApoB-100–Containing Lipoproteins
From the Department of Medical Biochemistry, Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Göteborg, Sweden.
Correspondence to Sven-Olof Olofsson, The Wallenberg Laboratory, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. E-mail Sven-Olof.Olofsson{at}medkem.gu.se
Objective— We investigated the role of ADP ribosylation factor 1 (ARF1) in the assembly of very-low-density lipoproteins (VLDLs).
Methods and Results— The dominant-negative ARF1 mutant, T31N, decreased the assembly of apoB-100 VLDL 1 (Svedberg floatation units [Sf] 60 to 400) by 80%. The decrease coincided with loss of coatamer I (COPI) from the Golgi apparatus and inhibition of anterograde transport, as demonstrated by time-lapse studies of the vesicular stomatitis virus G protein. The VLDL 1 assembly was also completely inhibited at 15°C. Thus, the antegrade transport is essential for the assembly of VLDL 1. Intracellular localization of N-acetylgalactosaminyl transferase 2 indicated that the Golgi apparatus was at least partly intact when the VLDL assembly was inhibited. Transient transfection with phospholipase D 1 increased the assembly of VLDL 1 and VLDL 2 (Sf 20 to 60). Overexpression of ARF1 in stably transfected McA-RH7777 cells increased the secretion of VLDL 2 but not of VLDL 1, which was dependent on the availability of oleic acid. Secretion of VLDL 1 increased with increasing amounts of oleic acid, and VLDL 2 secretion decreased simultaneously.
Conclusions— Overexpression of ARF1 increased the assembly of VLDL 2 but not of VLDL 1, whose production was dependent on both anterograde transport and the availability of fatty acids.
The assembly of VLDL depends on the ARF1-driven anterograde transport. Overexpression of ARF1 increases the secretion of VLDL 2 but not of VLDL 1, which is highly dependent on of fatty acids. The secretion of both VLDL 1 and VLDL 2 are increased by phospholipase D 1.
Key Words: ADP ribosylation factor 1 • apolipoprotein B • coatamer 1 • intracellular transport • very-low-density lipoproteins
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