Alpha-Catenin As a Tension Transducer That Induces Adherens Junction Development

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2010 May 11

PMID 20453849

Citations 509

Authors

Shigenobu Yonemura

Yuko Wada

Toshiyuki Watanabe

Akira Nagafuchi

Mai Shibata

Affiliations

Soon will be listed here.

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 alpha-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 alpha-catenin recruits vinculin, another main actin-binding protein of AJs, through force-dependent changes in alpha-catenin conformation. We identified regions in the alpha-catenin molecule that are required for its force-dependent binding of vinculin by introducing mutant alpha-catenin into cells and using in vitro binding assays. Fluorescence recovery after photobleaching analysis for alpha-catenin mobility and the existence of an antibody recognizing alpha-catenin in a force-dependent manner further supported the notion that alpha-catenin is a tension transducer that translates mechanical stimuli into a chemical response, resulting in AJ development.

Citing Articles

Actin-dependent α-catenin oligomerization contributes to adherens junction assembly.

Troyanovsky R, Indra I, Troyanovsky S Nat Commun. 2025; 16(1):1801.

PMID: 39979305 PMC: 11842732. DOI: 10.1038/s41467-025-57079-z.

Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature.

Gong R, Reynolds M, Sun X, Alushin G Sci Adv. 2025; 11(7):eadu0989.

PMID: 39951520 PMC: 11827635. DOI: 10.1126/sciadv.adu0989.

Crb3 and NF2: A dynamic duo that controls assembly of the apical junctions and barrier function via Rho/ROCK signaling.

Fan S, Varadarajan S, Garcia-Hernandez V, Margolis B, Parkos C, Nusrat A bioRxiv. 2025; .

PMID: 39868176 PMC: 11760739. DOI: 10.1101/2025.01.15.633166.

Advances in mechanotransduction and sonobiology: effects of audible acoustic waves and low-vibration stimulations on mammalian cells.

Del Rosario-Gilabert D, Valenzuela-Miralles A, Esquiva G Biophys Rev. 2025; 16(6):783-812.

PMID: 39830129 PMC: 11735818. DOI: 10.1007/s12551-024-01242-1.

Cadherins and growth factor receptors - ligand-selective mechano-switches at cadherin junctions.

Vu V, Sullivan B, Hebner E, Rahil Z, Zou Y, Leckband D J Cell Sci. 2025; 138(3).

PMID: 39817537 PMC: 11883276. DOI: 10.1242/jcs.262279.

References

Levi G, Gumbiner B, Thiery J . The distribution of E-cadherin during Xenopus laevis development. Development. 1991; 111(1):159-69. DOI: 10.1242/dev.111.1.159. View

Shewan A, Maddugoda M, Kraemer A, Stehbens S, Verma S, Kovacs E . Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts. Mol Biol Cell. 2005; 16(10):4531-42. PMC: 1237062. DOI: 10.1091/mbc.e05-04-0330. View

Torres M, Stoykova A, Huber O, Chowdhury K, Bonaldo P, Mansouri A . An alpha-E-catenin gene trap mutation defines its function in preimplantation development. Proc Natl Acad Sci U S A. 1997; 94(3):901-6. PMC: 19611. DOI: 10.1073/pnas.94.3.901. View

Pokutta S, Drees F, Takai Y, Nelson W, Weis W . Biochemical and structural definition of the l-afadin- and actin-binding sites of alpha-catenin. J Biol Chem. 2002; 277(21):18868-74. PMC: 3368618. DOI: 10.1074/jbc.M201463200. View

Johnson C, Tang H, Carag C, Speicher D, Discher D . Forced unfolding of proteins within cells. Science. 2007; 317(5838):663-6. PMC: 2741095. DOI: 10.1126/science.1139857. View

Pokutta S, Weis W . Structure and mechanism of cadherins and catenins in cell-cell contacts. Annu Rev Cell Dev Biol. 2007; 23:237-61. DOI: 10.1146/annurev.cellbio.22.010305.104241. View

Sawada Y, Tamada M, Dubin-Thaler B, Cherniavskaya O, Sakai R, Tanaka S . Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell. 2006; 127(5):1015-26. PMC: 2746973. DOI: 10.1016/j.cell.2006.09.044. View

Kobielak A, Fuchs E . Alpha-catenin: at the junction of intercellular adhesion and actin dynamics. Nat Rev Mol Cell Biol. 2004; 5(8):614-25. PMC: 2475680. DOI: 10.1038/nrm1433. View

Ivanov A, Bachar M, Babbin B, Adelstein R, Nusrat A, Parkos C . A unique role for nonmuscle myosin heavy chain IIA in regulation of epithelial apical junctions. PLoS One. 2007; 2(7):e658. PMC: 1920554. DOI: 10.1371/journal.pone.0000658. View

10.

Tsukita S, Furuse M, Itoh M . Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001; 2(4):285-93. DOI: 10.1038/35067088. View

11.

Imamura Y, Itoh M, Maeno Y, Tsukita S, Nagafuchi A . Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion. J Cell Biol. 1999; 144(6):1311-22. PMC: 2150587. DOI: 10.1083/jcb.144.6.1311. View

12.

Gloushankova N, Krendel M, Alieva N, Bonder E, Feder H, Vasiliev J . Dynamics of contacts between lamellae of fibroblasts: essential role of the actin cytoskeleton. Proc Natl Acad Sci U S A. 1998; 95(8):4362-7. PMC: 22494. DOI: 10.1073/pnas.95.8.4362. View

13.

Janssen M, Kim E, Liu H, Fujimoto L, Bobkov A, Volkmann N . Three-dimensional structure of vinculin bound to actin filaments. Mol Cell. 2006; 21(2):271-81. DOI: 10.1016/j.molcel.2005.11.020. View

14.

Uchida N, Imamura Y, Nagafuchi A, Fujimoto K, Uemura T, Vermeulen S . alpha-Catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells. J Cell Biol. 1998; 142(3):847-57. PMC: 2148175. DOI: 10.1083/jcb.142.3.847. View

15.

Watabe M, Nagafuchi A, Tsukita S, Takeichi M . Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line. J Cell Biol. 1994; 127(1):247-56. PMC: 2120192. DOI: 10.1083/jcb.127.1.247. View

16.

Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S . Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002; 420(6915):563-73. DOI: 10.1038/nature01266. View

17.

Lecuit T, Lenne P . Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nat Rev Mol Cell Biol. 2007; 8(8):633-44. DOI: 10.1038/nrm2222. View

18.

Vasioukhin V, Bauer C, Degenstein L, Wise B, Fuchs E . Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell. 2001; 104(4):605-17. DOI: 10.1016/s0092-8674(01)00246-x. View

19.

Straight A, Cheung A, Limouze J, Chen I, Westwood N, Sellers J . Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor. Science. 2003; 299(5613):1743-7. DOI: 10.1126/science.1081412. View

20.

Martin P, Parkhurst S . Parallels between tissue repair and embryo morphogenesis. Development. 2004; 131(13):3021-34. DOI: 10.1242/dev.01253. View