@article{e5b7ef73972b4570b1ef2ed2fc7f3e5b,
title = "Identification and characterization of Crumbs polarity complex proteins in Caenorhabditis elegans",
abstract = "Crumbs proteins are evolutionarily conserved transmembrane proteins with essential roles in promoting the formation of the apical domain in epithelial cells. The short intracellular tail of Crumbs proteins are known to interact with several proteins, including the scaffolding protein PALS1 (protein associated with LIN7, Stardust in Drosophila). PALS1 in turn binds to a second scaffolding protein PATJ (PALS1-associated tight junction protein) to form the core Crumbs/PALS1/PATJ complex. While essential roles in epithelial organization have been shown for Crumbs proteins in Drosophila and mammalian systems, the three Caenorhabditis elegans crumbs genes are dispensable for epithelial polarization and development. Here, we investigated the presence and function of PALS1 and PATJ orthologs in C. elegans. We identified MAGU-2 as the C. elegans ortholog of PALS1 and show that MAGU-2 interacts with all three Crumbs proteins and localizes to the apical membrane domain of intestinal epithelial cells in a Crumbs-dependent fashion. Similar to crumbs mutants, magu-2 deletion showed no epithelial polarity defects. We also identified MPZ-1 as a candidate ortholog of PATJ based on the physical interaction with MAGU-2 and sequence similarity with PATJ proteins. However, MPZ-1 is not broadly expressed in epithelial tissues and, therefore, not likely a core component of the C. elegans Crumbs complex. Finally, we show overexpression of the Crumbs proteins EAT-20 or CRB-3 can lead to apical membrane expansion in the intestine. Our results shed light on the composition of the C. elegans Crumbs complex and indicate that the role of Crumbs proteins in promoting apical domain formation is conserved.",
keywords = "C. elegans, cell polarity, Crb, Crumbs, epithelial polarity, MAGU-2, MPZ-1, PALS1, PATJ, Stardust",
author = "Castiglioni, {Victoria G.} and Ramalho, {Jo{\~a}o J.} and Kroll, {Jason R.} and Riccardo Stucchi and {van Beuzekom}, Hanna and Ruben Schmidt and Maarten Altelaar and Mike Boxem",
note = "Funding Information: This work was supported by the Netherlands Organization for Scientific Research (NWO)-ALW Open Program 824.14.021 and NWO -VICI 016.VICI.170.165 grants to M. B. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: We thank members of the S van den Heuvel and M Boxem groups for helpful discussions. We also thank Wormbase ( 89 ) 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 European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement No. 675407 – PolarNet. This research also was part of the Netherlands X-omics Initiative and partially funded by NWO (Project 184.034.019 ). Funding Information: We thank members of the S van den Heuvel and M Boxem groups for helpful discussions. We also thank Wormbase (89) 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 European Union's Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No. 675407 ? PolarNet. This research also was part of the Netherlands X-omics Initiative and partially funded by NWO (Project 184.034.019). V. G. C. J. J. R. and M. B. conceptualization; V. G. C. J. J. R. J. R. K. Riccardo Stucchi, and H. v. B. formal analysis; V. G. C. J. J. R. J. R. K. Riccardo Stucchi, H. v. B. and Ruben Schmidt investigation; M. A. and M. B. resources; V. G. C. data curation; V. G. C. writing?original draft; V. G. C. J. J. R. J. R. K. Riccardo Stucchi, Ruben Schmidt, M. A. and M. B. writing?review and editing; V. G. C. and M. B. visualization; V. G. C. and M. B. supervision; M. B. project administration; M. A. and M. B. funding acquisition. This work was supported by the Netherlands Organization for Scientific Research (NWO)-ALW Open Program 824.14.021 and NWO-VICI 016.VICI.170.165 grants to M. B. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = apr,
doi = "10.1016/j.jbc.2022.101786",
language = "English",
volume = "298",
pages = "1--16",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "4",
}