Abstract
The function of epithelial cell sheets depends on the integrity of specialized cell–cell junctions that connect neighbouring cells. We have characterized the novel coiled-coil protein AJM-1, which localizes to an apical junctional domain of Caenorhabditis elegans epithelia basal to the HMR–HMP (cadherin–catenin) complex. In the absence of AJM-1, the integrity of this domain is compromised. Proper AJM-1 localization requires LET-413 and DLG-1, homologues of the Drosophila tumour suppressors Scribble and Discs large, respectively. DLG-1 physically interacts with AJM-1 and is required for its normal apical distribution, and LET-413 mediates the rapid accumulation of both DLG-1 and AJM-1 in the apical domain. In the absence of both dlg-1 and let-413 function AJM-1 is almost completely lost from apical junctions in embryos, whereas HMP-1 (α-catenin) localization is only mildly affected. We conclude that LET-413 and DLG-1 cooperatively control AJM-1 localization and that AJM-1 controls the integrity of a distinct apical junctional domain in C. elegans.
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Acknowledgements
We thank members of the Hardin laboratory for helpful discussion and critical reading of the manuscript, J. Pawley for help with confocal microscopy, and the Wickens laboratory, in particular D. Bernstein, for technical assistance with two-hybrid experiments and the GST pull-down assay. This work was supported by NSF grant DBI97-24515 and NIH grant GM58038 awarded to J.D.H. The Bio-Rad MRC 1024 confocal microscope is supported by NSF grant 9724515.
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Köppen, M., Simske, J., Sims, P. et al. Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia. Nat Cell Biol 3, 983–991 (2001). https://doi.org/10.1038/ncb1101-983
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DOI: https://doi.org/10.1038/ncb1101-983
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