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α-Catenin as a tension transducer that induces adherens junction development

Abstract

Adherens junctions (AJs), which are organized by adhesion proteins and the underlying actin cytoskeleton, probably sense pulling forces from adjacent cells and modulate opposing forces to maintain tissue integrity, but the regulatory mechanism remains unknown at the molecular level. Although the possibility that α-catenin acts as a direct linker between the membrane and the actin cytoskeleton for AJ formation and function has been minimized, here we show that α-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in α-catenin conformation. We identified regions in the α-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant α-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for α-catenin mobility and the existence of an antibody recognizing α-catenin in a force-dependent manner further supported the notion that α-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.

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Figure 1: Myosin II-B localization in AJ regions in epithelial cells.
Figure 2: Molecular dissection of α-catenin to identify regions responsible for force-dependent recruitment of vinculin.
Figure 3: Proposed molecular mechanism of force-dependent binding of vinculin to α-catenin.
Figure 4: Stabilization of α-catenin by actomyosin forces revealed by FRAP measurements.
Figure 5: Membrane-anchored α-catenin also shows force-dependent vinculin binding.
Figure 6: Preferential binding of α18 to α-catenin in the vinculin-binding form.
Figure 7: Dissociation of homophilic cadherin binding abrogates both α18 binding and vinculin accumulation.
Figure 8: Experimental increase in forces applied on AJs causes changes in α-catenin conformation and enhances AJ development.

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Acknowledgements

We thank F. van Roy, E. Reichman and the Health Science Research Resources Bank for cells; M. Takeichi for cells, antibodies and plasmids; Sa. Tsukita for antibodies; R. Y. Tsien (Howard Hughes Medical Institute, University of California San Diego) for a plasmid; M. Furuse for discussions; and T. Hakoshima and H. Hiraga for critical reading of the manuscript. We also thank Y. Hayashizaki (RIKEN GSC) for a mouse vinculin complementary DNA from FANTOM2 clones. This work was supported by grants-in-aid for Exploratory Research (18657065) and Scientific Research in Priority Areas (17048034) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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S.Y. designed the experiments. S.Y., Y.W., T.W., A.N. and M.S. performed experiments. S.Y. analysed the data and wrote the manuscript.

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Correspondence to Shigenobu Yonemura.

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Yonemura, S., Wada, Y., Watanabe, T. et al. α-Catenin as a tension transducer that induces adherens junction development. Nat Cell Biol 12, 533–542 (2010). https://doi.org/10.1038/ncb2055

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