Universität zu Köln

Coch, Richard A., Geisler, Florian, Annibal, Andrea ORCID: 0000-0003-4311-5417, Antebi, Adam and Leube, Rudolf E. (2020). Identification of A Novel Link between the Intermediate Filament Organizer IFO-1 and Cholesterol Metabolism in the Caenorhabditis elegans Intestine. Int. J. Mol. Sci., 21 (21). BASEL: MDPI. ISSN 1422-0067

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Abstract

The intestine is an organ essential to organismal nutrient absorption, metabolic control, barrier function and immunoprotection. The Caenorhabditis elegans intestine consists of 20 cells harboring a dense intermediate filament network positioned below the apical plasma membrane that forms a junction-anchored sheath around the intestinal lumen. This evolutionarily conserved arrangement provides mechanical and overall stress-protection, and it serves as an important model for deciphering the role of intestinal architecture in metazoan biology. We recently reported that the loss-of-function mutation of the intestinal intermediate filament organizer IFO-1 perturbs this architecture, leading to reduced body size and reproduction. Here, we demonstrate that the IFO-1 mutation dramatically affects cholesterol metabolism. Mutants showed an increased sensitivity to cholesterol depletion, reduced cholesterol uptake, and cholesterol transfer to the gonads, which is also observed in worms completely lacking an intermediate filament network. Accordingly, we found striking similarities to transcriptome and lipidome profiles of a nuclear hormone receptor (NHR)-8 mutant. NHR-8 is homologous to mammalian LXR (liver X receptor) that serves as a sterol sensor and transcriptional regulator of lipid metabolism. Remarkably, increasing exogenous cholesterol partially rescues the developmental retardation in IFO-1 mutants. Our results uncover a novel link of the intestinal intermediate filament cytoskeleton to cholesterol metabolism that contributes to compromised growth and reproduction.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Coch, Richard A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Geisler, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Annibal, Andrea UNSPECIFIED orcid.org/0000-0003-4311-5417 UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED Leube, Rudolf E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-313495
DOI:	10.3390/ijms21218219
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	21
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language C. ELEGANS; DAUER FORMATION; VIMENTIN; REPRODUCTION; TRAFFICKING; REQUIREMENT; EXPRESSION; TRANSPORT; PROTEIN; C1 Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31349