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A novel function for the MAP kinase SMA-5 in intestinal tube stability.

Geisler, Florian and Gerhardus, Harald and Carberry, Katrin and Davis, Wayne and Jorgensen, Erik and Richardson, Christine and Bossinger, Olaf and Leube, Rudolf E. (2016) 'A novel function for the MAP kinase SMA-5 in intestinal tube stability.', Molecular biology of the cell., 27 (24). pp. 3855-3868.

Abstract

Intermediate filaments are major cytoskeletal components whose assembly into complex networks and isotype-specific functions are still largely unknown. Caenorhabditis elegans provides an excellent model system to study intermediate filament organization and function in vivo. Its intestinal intermediate filaments localize exclusively to the endotube, a circumferential sheet just below the actin-based terminal web. A genetic screen for defects in the organization of intermediate filaments identified a mutation in the catalytic domain of the MAP kinase 7 orthologue sma-5(kc1). In sma-5(kc1) mutants, pockets of lumen penetrate the cytoplasm of the intestinal cells. These membrane hernias increase over time without affecting epithelial integrity and polarity. A more pronounced phenotype was observed in the deletion allele sma-5(n678) and in intestine-specific sma-5(RNAi). Besides reduced body length, an increased time of development, reduced brood size, and reduced life span were observed in the mutants, indicating compromised food uptake. Ultrastructural analyses revealed that the luminal pockets include the subapical cytoskeleton and coincide with local thinning and gaps in the endotube that are often enlarged in other regions. Increased intermediate filament phosphorylation was detected by two-dimensional immunoblotting, suggesting that loss of SMA-5 function leads to reduced intestinal tube stability due to altered intermediate filament network phosphorylation.

Item Type:Article
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Status:Peer-reviewed
Publisher Web site:https://doi.org/10.1091/mbc.E16-02-0099
Publisher statement:© 2016 Geisler et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Date accepted:05 October 2016
Date deposited:16 December 2016
Date of first online publication:12 October 2016
Date first made open access:No date available

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