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The intestinal intermediate filament network responds to and protects against microbial insults and toxins

Geisler, Florian; Coch, Richard A.; Richardson, Christine; Goldberg, Martin; Denecke, Bernd; Bossinger, Olaf; Leube, Rudolf E.

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Authors

Florian Geisler

Richard A. Coch

Christine Richardson

Bernd Denecke

Olaf Bossinger

Rudolf E. Leube



Abstract

The enrichment of intermediate filaments in the apical cytoplasm of intestinal cells is evolutionary conserved forming a sheath that is anchored to apical junctions and positioned below the microvillar brush border suggestive of a protective intracellular barrier function. To test this, we used C. elegans, whose intestinal cells are endowed with a particularly dense intermediate filament-rich layer that is referred to as the endotube. We find alterations in endotube structure and intermediate filament expression upon infection with nematicidal Bacillus thuringiensis or treatment with its major pore-forming toxin crystal protein Cry5B. Endotube impairment due to defined genetic mutations of intermediate filaments and their regulators results in increased Cry5B sensitivity as evidenced by elevated larval arrest, prolonged time of larval development and reduced survival. Phenotype severity reflects the severity of endotube alterations and correlates with reduced rescue upon toxin removal. The results provide in vivo evidence for a major protective role of a properly configured intermediate filament network as an intracellular barrier in intestinal cells. This notion is further supported by increased sensitivity of endotube mutants to oxidative and osmotic stress.

Citation

Geisler, F., Coch, R. A., Richardson, C., Goldberg, M., Denecke, B., Bossinger, O., & Leube, R. E. (2019). The intestinal intermediate filament network responds to and protects against microbial insults and toxins. Development, 146(2), Article dev.169482. https://doi.org/10.1242/dev.169482

Journal Article Type Article
Acceptance Date Dec 19, 2018
Online Publication Date Jan 23, 2019
Publication Date Jan 15, 2019
Deposit Date Jan 14, 2019
Publicly Available Date Jan 23, 2020
Journal Development.
Print ISSN 0950-1991
Electronic ISSN 1477-9129
Publisher The Company of Biologists
Peer Reviewed Peer Reviewed
Volume 146
Issue 2
Article Number dev.169482
DOI https://doi.org/10.1242/dev.169482

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