Intermediate filament network perturbation in the C. elegans intestine causes systemic dysfunctions
- RWTH Aachen University, Germany
- Utrecht University, Netherlands
- Universitätsklinikum Aachen, Germany
Abstract
Intermediate filaments (IFs) are major components of the metazoan cytoskeleton. A long-standing debate concerns the question whether IF network organization only reflects or also determines cell and tissue function. Using C. elegans, we have recently described mutants of the MAPK SMA-5 which perturb the organization of the intestinal IF cytoskeleton resulting in luminal widening and cytoplasmic invaginations. Besides these structural phenotypes, systemic dysfunctions were also observed. We now identify the IF polypeptide IFB-2 as a highly efficient suppressor of both the structural and functional deficiencies of sma-5 animals, by removing the aberrant IF network. Mechanistically, perturbed IF network morphogenesis is linked to hyperphosphorylation of multiple sites throughout the entire IFB-2 molecule. The rescuing capability is IF isotype-specific and not restricted to SMA-5 mutants but extends to mutants that disrupt the function of the cytoskeletal linker IFO-1 and the IF-associated protein BBLN1. The findings provide strong evidence for adverse consequences of the deranged IF networks with implications for diseases that are characterized by altered IF network organization.
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Funding
Deutsche Forschungsgemeinschaft (LE566/14-1,3)
- Rudolf E Leube
Nederlandse Organisatie voor Wetenschappelijk Onderzoek ((NWO)-VICI 016.VICI.170.165)
- Mike Boxem
Deutsche Forschungsgemeinschaft (INST 948/4S-1)
- Vera Jankowski
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Geisler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Intermediate filament network perturbation in the C. elegans intestine causes systemic dysfunctions
eLife 12:e82333.
https://doi.org/10.7554/eLife.82333
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