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The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2012 Jul 15; Vol. 21 (14), pp. 3128-42. Date of Electronic Publication: 2012 Apr 14. - Publication Year :
- 2012
-
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.
- Subjects :
- ADP-Ribosylation Factors genetics
Animals
Apolipoprotein A-I metabolism
GTP Phosphohydrolases genetics
Golgi Apparatus metabolism
Humans
Intestinal Mucosa metabolism
Lipid Metabolism
Mice
Mice, Knockout
Protein Binding
Protein Transport
rab2 GTP-Binding Protein genetics
rab2 GTP-Binding Protein metabolism
ADP-Ribosylation Factors metabolism
Chylomicrons metabolism
GTP Phosphohydrolases metabolism
Golgi Apparatus enzymology
Intestinal Mucosa enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 21
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 22505585
- Full Text :
- https://doi.org/10.1093/hmg/dds140