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Distinct β-catenins mediate adhesion and signalling functions in C. elegans

Abstract

In flies and vertebrates, Armadillo/β-catenin forms a complex with Tcf/Lef-1 transcription factors, serving as an essential co-activator to mediate Wnt signalling. It also associates with cadherins to mediate adhesion. In Caenorhabditis elegans, three putative β-catenin homologues have been identified: WRM-1, BAR-1 and HMP-2. WRM-1 and the Tcf homologue POP-1 mediate Wnt signalling by a mechanism that has challenged current views of the Wnt pathway1,2,3. Here we show that BAR-1 is the only β-catenin homologue that interacts directly with POP-1. BAR-1 mediates Wnt signalling by forming a BAR-1/POP-1 bipartite transcription factor that activates expression of Wnt target genes such as the Hox gene mab-5. HMP-2 is the only β-catenin homologue that interacts with the single cadherin of C. elegans, HMR-1. We conclude that a canonical Wnt pathway exists in C. elegans. Furthermore, our analysis shows that the functions of C. elegans β-catenins in adhesion and in signalling are performed by separate proteins.

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Figure 1: POP-1 is a functional Tcf homologue.
Figure 2: Physical interactions between the three C. elegans β-catenins and POP-1 and HMR-1.
Figure 3: POP-1 and BAR-1 activate transcription of a Tcf reporter gene.
Figure 4: Expression of ΔN-POP-1 inhibits mab-5 expression.
Figure 5: The signalling and adhesion functions of Armadillo/β-catenin are distributed over three different β-catenin homologues in C. elegans .

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Acknowledgements

We thank L. Meyaard for critically reading the manuscript and members of the Clevers laboratory for helpful discussions; C. Kenyon for the mab-5 reporter muIs2; Q. Ch’ng and C. Kenyon for tips on staining muIs2 animals for β-galactosidase expression; and A. Fire for pPD49.78. This work was supported in part by an NIH grant to M.H and PIONEER and Program grants from NWO Medische Wefenschappen to H.C.

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Correspondence to Hendrik C. Korswagen.

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Korswagen, H., Herman, M. & Clevers, H. Distinct β-catenins mediate adhesion and signalling functions in C. elegans. Nature 406, 527–532 (2000). https://doi.org/10.1038/35020099

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