The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium.
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The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium. / Jaschke, Alexander; Chung, Bomee; Hesse, Deike; Kluge, Reinhart; Zahn, Claudia; Moser, Markus; Petzke, Klaus-Jürgen; Brigelius-Flohé, Regina; Puchkov, Dmytro; Koepsell, Hermann; Heeren, Jörg; Joost, Hans-Georg; Schürmann, Annette.
In: HUM MOL GENET, Vol. 21, No. 14, 14, 2012, p. 3128-3142.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium.
AU - Jaschke, Alexander
AU - Chung, Bomee
AU - Hesse, Deike
AU - Kluge, Reinhart
AU - Zahn, Claudia
AU - Moser, Markus
AU - Petzke, Klaus-Jürgen
AU - Brigelius-Flohé, Regina
AU - Puchkov, Dmytro
AU - Koepsell, Hermann
AU - Heeren, Jörg
AU - Joost, Hans-Georg
AU - Schürmann, Annette
PY - 2012
Y1 - 2012
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 chylo-microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells.
AB - 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.
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Lipid Metabolism
KW - Protein Transport
KW - Protein Binding
KW - GTP Phosphohydrolases/genetics/metabolism
KW - ADP-Ribosylation Factors/genetics/metabolism
KW - Apolipoprotein A-I/metabolism
KW - Chylomicrons/metabolism
KW - Golgi Apparatus/enzymology/metabolism
KW - Intestinal Mucosa/enzymology/metabolism
KW - rab2 GTP-Binding Protein/genetics/metabolism
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Lipid Metabolism
KW - Protein Transport
KW - Protein Binding
KW - GTP Phosphohydrolases/genetics/metabolism
KW - ADP-Ribosylation Factors/genetics/metabolism
KW - Apolipoprotein A-I/metabolism
KW - Chylomicrons/metabolism
KW - Golgi Apparatus/enzymology/metabolism
KW - Intestinal Mucosa/enzymology/metabolism
KW - rab2 GTP-Binding Protein/genetics/metabolism
M3 - SCORING: Journal article
VL - 21
SP - 3128
EP - 3142
JO - HUM MOL GENET
JF - HUM MOL GENET
SN - 0964-6906
IS - 14
M1 - 14
ER -