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Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia

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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Figure 1: ajm-1 encodes a novel coiled-coil protein.
Figure 2: AJM-1 localizes to a distinct apical domain of epithelial junctions.
Figure 3: ajm-1(ok160) embryos are arrested at the twofold stage and display compromised integrity of apical junctions.
Figure 4: AJM-1 and DLG-1 physically interact and function in a common pathway.
Figure 5: LET-413 and DLG-1 cooperatively control AJM-1 localization.
Figure 6: LET-413 is required for rapid apical confinement of DLG-1.
Figure 7: Model for the control of AJM-1 localization by LET-413 and DLG-1.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Data deposits

  • The GenBank accession numbers for the C25A11.4 (ajm-1) sequence and the dlg-1 sequence are U39650 and AJ295228, respectively.

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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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Correspondence to Jeffrey D. Hardin.

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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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