title: The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium.
abstract: 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 chylo-microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells.
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, D-14558 Nuthetal, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jaschke
authors.forename: Bomee
authors.initials: B
authors.lastname: Chung
authors.forename: Deike
authors.initials: D
authors.lastname: Hesse
authors.forename: Reinhart
authors.initials: R
authors.lastname: Kluge
authors.forename: Claudia
authors.initials: C
authors.lastname: Zahn
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.forename: Klaus-Jürgen
authors.initials: KJ
authors.lastname: Petzke
authors.forename: Regina
authors.initials: R
authors.lastname: Brigelius-Flohé
authors.forename: Dmytro
authors.initials: D
authors.lastname: Puchkov
authors.forename: Hermann
authors.initials: H
authors.lastname: Koepsell
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D021381:Protein Transport; D020693:rab2 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D002914:Chylomicrons; D020558:GTP Phosphohydrolases; D020727:ADP-Ribosylation Factors; C541296:ARFRP1 protein, human; C531986:Arfrp1 protein, mouse; D020693:rab2 GTP-Binding Protein