BBLN-1 is essential for intermediate filament organization and apical membrane morphology
Remmelzwaal, Sanne; Geisler, Florian; Stucchi, Riccardo; van der Horst, Suzanne; Pasolli, Milena; Kroll, Jason R.; Jarosinska, Olga D.; Akhmanova, Anna; Richardson, Christine A.; Altelaar, Maarten; Leube, Rudolf E.; Ramalho, João J.; Boxem, Mike
(2021) Current Biology, volume 31, issue 11, pp. 2334 - 2346.e9
(Article)
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
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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.
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Keywords: BBLN, BBLN-1, bublin, C. elegans, epithelial tube, intermediate filaments, intestine, General Neuroscience, General Biochemistry,Genetics and Molecular Biology, General Agricultural and Biological Sciences
ISSN: 0960-9822
Publisher: Cell Press
Note: Funding Information: We thank R. Schmidt for sharing strain BOX459, V. Garcia Castiglioni for strains BOX251 and BOX260, K. Oegema for strain OD2509, J. Sepers for the NRFL-1::mCherry fusion, and B. van der Vaart for the keratin plasmids. We thank M. Kersten, J.-P. ten Klooster, W. Nijenhuis, and N. Schwarz for technical assistance. We thank S. van den Heuvel, S. Ruijtenberg, M. Harterink, B. Mulder, B. Snel, and members of the van den Heuvel and Boxem groups for helpful discussions. We also thank WormBase, the HUGO Gene Nomenclature Committee (HGNC), and the Biology Imaging Center, Faculty of Sciences, Department of Biology, Utrecht University. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This work was supported by the Netherlands Organisation for Scientific Research (NWO)-CW ECHO 711.014.005 and NWO-VICI 016.VICI.170.165 grants to M.B. the German Research Council (LE566/14-1, 3; R.E.L.), and the START Program of the Medical Faculty of RWTH Aachen University (131/20; F.G.). This research was part of the Netherlands X-omics Initiative and partially funded by NWO, project 184.034.019. Conceptualization, S.R. J.J.R. and M.B.; Formal Analysis, S.R. R.S. and M.B.; Investigation, S.R. F.G. R.S. J.R.K. S.v.d.H. O.D.J. M.P. and J.J.R.; Resources, S.v.d.H. A.A. C.A.R. M.A. R.E.L. and M.B.; Data Curation, S.R. and J.R.K.; Writing ? Original Draft, S.R. J.J.R. and M.B.; Writing ? Review & Editing, F.G. A.A. C.A.R. and R.E.L.; Visualization, S.R. and M.B.; Supervision, S.R. F.G. A.A. C.A.R. M.A. R.E.L. J.J.R. and M.B.; Project Administration, M.B.; Funding Acquisition, F.G. A.A. C.A.R. M.A. R.E.L. and M.B. The authors declare no competing interests. Funding Information: We thank R. Schmidt for sharing strain BOX459, V. Garcia Castiglioni for strains BOX251 and BOX260, K. Oegema for strain OD2509, J. Sepers for the NRFL-1::mCherry fusion, and B. van der Vaart for the keratin plasmids. We thank M. Kersten, J.-P. ten Klooster, W. Nijenhuis, and N. Schwarz for technical assistance. We thank S. van den Heuvel, S. Ruijtenberg, M. Harterink, B. Mulder, B. Snel, and members of the van den Heuvel and Boxem groups for helpful discussions. We also thank WormBase, the HUGO Gene Nomenclature Committee (HGNC), and the Biology Imaging Center, Faculty of Sciences, Department of Biology, Utrecht University. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ). This work was supported by the Netherlands Organisation for Scientific Research (NWO)-CW ECHO 711.014.005 and NWO -VICI 016.VICI.170.165 grants to M.B., the German Research Council ( LE566/14-1, 3 ; R.E.L.), and the START Program of the Medical Faculty of RWTH Aachen University ( 131/20; F.G. ). This research was part of the Netherlands X-omics Initiative and partially funded by NWO , project 184.034.019 . Publisher Copyright: © 2021 The Author(s)
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