Intermediate filament network perturbation in the C. elegans intestine causes systemic dysfunctions

  1. Florian Geisler
  2. Sanne Remmelzwaal
  3. Vera Jankowski
  4. Ruben Schmidt
  5. Mike Boxem
  6. Rudolf E Leube  Is a corresponding author
  1. RWTH Aachen University, Germany
  2. Utrecht University, Netherlands
  3. 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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Article and author information

Author details

  1. Florian Geisler

    Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Sanne Remmelzwaal

    Department of Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Vera Jankowski

    Institute for Molecular Cardiovascular Research, Universitätsklinikum Aachen, Aachen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Ruben Schmidt

    Department of Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9187-5424
  5. Mike Boxem

    Department of Biology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3966-4173
  6. Rudolf E Leube

    Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Aachen, Germany
    For correspondence
    rleube@ukaachen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5519-7379

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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  1. Florian Geisler
  2. Sanne Remmelzwaal
  3. Vera Jankowski
  4. Ruben Schmidt
  5. Mike Boxem
  6. Rudolf E Leube
(2023)
Intermediate filament network perturbation in the C. elegans intestine causes systemic dysfunctions
eLife 12:e82333.
https://doi.org/10.7554/eLife.82333

Share this article

https://doi.org/10.7554/eLife.82333

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