Journal Article

The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium

Alexander Jaschke, Bomee Chung, Deike Hesse, Reinhart Kluge, Claudia Zahn, Markus Moser, Klaus-Jürgen Petzke, Regina Brigelius-Flohé, Dmytro Puchkov, Hermann Koepsell, Joerg Heeren, Hans-Georg Joost and Annette Schürmann

in Human Molecular Genetics

Volume 21, issue 14, pages 3128-3142
Published in print July 2012 | ISSN: 0964-6906
Published online April 2012 | e-ISSN: 1460-2083 | DOI:

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The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium. Mice lacking Arfrp1 specifically in the intestine (Arfrp1vil−/−) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. Arfrp1vil−/− enterocytes as well as Arfrp1 mRNA depleted Caco-2 cells absorbed fatty acids normally but secreted chylomicrons with a markedly reduced triacylglycerol content. In addition, the release of apolipoprotein A-I (ApoA-I) was dramatically decreased, and ApoA-I accumulated in the Arfrp1vil−/− epithelium, where it predominantly co-localized with Rab2. The release of chylomicrons from Caco-2 was markedly reduced after the suppression of Rab2, ARL1 and Golgin-245. Thus, the GTPase ARFRP1 and its downstream proteins are required for the lipidation of chylo­microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells.

Journal Article.  6956 words.  Illustrated.

Subjects: Genetics and Genomics

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