on December 23, 2004
Published online before print December 23, 2004, doi: 10.1161/01.ATV.0000154135.21689.47
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Submitted on August 19, 2004
Accepted on December 1, 2004
Role of ADP Ribosylation Factor 1 in the Assembly and Secretion of ApoB-100-Containing Lipoproteins
Lennart Asp ;
From the Department of Medical Biochemistry, Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Göteborg, Sweden.
* To whom correspondence should be addressed. 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 (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.
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