2. Academic Validation
  3. BBLN-1 is essential for intermediate filament organization and apical membrane morphology

BBLN-1 is essential for intermediate filament organization and apical membrane morphology

  • Curr Biol. 2021 Jun 7;31(11):2334-2346.e9. doi: 10.1016/j.cub.2021.03.069.
Sanne Remmelzwaal 1,  Florian Geisler 2,  Riccardo Stucchi 3,  Suzanne van der Horst 4,  Milena Pasolli 5,  Jason R Kroll 1,  Olga D Jarosinska 1,  Anna Akhmanova 5,  Christine A Richardson 6,  Maarten Altelaar 7,  Rudolf E Leube 2,  João J Ramalho 8,  Mike Boxem 9
Affiliations

Affiliations

  • 1 Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
  • 2 Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany.
  • 3 Cell Biology, Neurobiology and Biophysics, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
  • 4 Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • 5 Cell Biology, Neurobiology and Biophysics, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
  • 6 Department of Biosciences, Durham University, Durham, UK.
  • 7 Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
  • 8 Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands. Electronic address: [email protected].
  • 9 Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands. Electronic address: [email protected].
PMID: 33857431 DOI: 10.1016/j.cub.2021.03.069
Abstract

Epithelial tubes are essential components of metazoan organ systems that control the flow of fluids and the exchange of Materials between body compartments and the outside environment. The size and shape of the central lumen confer important characteristics to tubular organs and need to be carefully controlled. Here, we identify the small coiled-coil protein BBLN-1 as a regulator of lumen morphology in the C. elegans intestine. Loss of BBLN-1 causes the formation of bubble-shaped invaginations of the apical membrane into the cytoplasm of intestinal cells and abnormal aggregation of the subapical intermediate filament (IF) network. BBLN-1 interacts with IF proteins and localizes to the IF network in an IF-dependent manner. The appearance of invaginations is a result of the abnormal IF aggregation, indicating a direct role for the IF network in maintaining lumen homeostasis. Finally, we identify bublin (BBLN) as the mammalian ortholog of BBLN-1. When expressed in the C. elegans intestine, BBLN recapitulates the localization pattern of BBLN-1 and can compensate for the loss of BBLN-1 in early larvae. In mouse intestinal organoids, BBLN localizes subapically, together with the IF protein keratin 8. Our results therefore may have implications for understanding the role of IFs in regulating epithelial tube morphology in mammals.

Keywords

BBLN; BBLN-1; C. elegans; bublin; epithelial tube; intermediate filaments; intestine.

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