TY - JOUR A1 - Jaschke, Alexander A1 - Chung, Bomee A1 - Hesse, Deike A1 - Kluge, Reinhart A1 - Zahn, Claudia A1 - Moser, Markus A1 - Petzke, Klaus-Jürgen A1 - Brigelius-Flohé, Regina A1 - Puchkov, Dmytro A1 - Koepsell, Hermann A1 - Heeren, Joerg A1 - Joost, Hans-Georg A1 - Schürmann, Annette T1 - The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium T2 - Human Molecular Genetics N2 - 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 \((Arfrp1^{vil−/−})\) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. \(Arfrp1^{vil−/−}\) 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 \(Arfrp1^{vil−/−}\) 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. KW - ARF Y1 - 2012 UR - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/12565 UR - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-125658 VL - 21 IS - 14 ER -