An Autoinhibited Structure of α-Catenin and Its Implications for Vinculin Recruitment to Adherens Junctions

Ishiyama, Noboru; Tanaka, Nobutoshi; Abe, Kentaro; Yang, Yoo Jeong; Abbas, Y.M.; Umitsu, Masatomo; Nagar, Bhushan; Bueler, Stephanie A.; Rubinstein, John L.; Takeichi, Masatoshi; Ikura, Mitsuhiko

doi:10.1074/jbc.m113.453928

Cited by 111 publications

(190 citation statements)

References 67 publications

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“…In both, there are intramolecular interactions between the actin-binding and N II domains, but the position of the actin-binding domain differs by a rotation of almost 180°. In contrast, the ABD is completely disordered in another ␣E-catenin dimer structure (18), consistent with it being flexibly linked to the rest of the protein in solution. There is no crystal structure of a monomeric ␣-catenin or of full-length ␣-catenin bound to ␤-catenin, so the position of the ABD with respect to the rest of the protein is not known.…”

Section: Protein Constructsmentioning

confidence: 81%

“…In contrast, ␣N-catenin homodimerization shows a strong temperature dependence: the K d for homodimerization is 45 M at 25°C and 2 M at 37°C (Table 2). No dimerization was observed at 4°C by Ishiyama et al (18), which led to the conclusion that ␣N-catenin is a monomer. The data here, however, demonstrate that at physiological temperatures ␣N-catenin can dimerize readily.…”

Section: Resultsmentioning

confidence: 99%

“…The ABD also binds to EPLIN (12) and to the tight junction protein ZO-1 (13,14). The ABD was disordered in a crystal structure of fulllength ␣E-catenin (18), implying that it is flexibly linked to the rest of the protein. However, another structure of near-fulllength ␣E-catenin (missing the first 82 residues) showed that the ABD packs against portions of the N and M regions, although in the two crystallographically independent copies, the position of the ABD is different (20).…”

Section: Domain (Abd)mentioning

confidence: 99%

See 2 more Smart Citations

Structural and Thermodynamic Characterization of Cadherin·β-Catenin·α-Catenin Complex Formation

Pokutta

Choi

Ahlsén

et al. 2014

Journal of Biological Chemistry

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Background: Cadherin cell adhesion molecules are linked to the actin cytoskeleton by the proteins ␤-and ␣-catenin. Results: The interactions of ␣-catenins in the cadherin⅐␤-catenin⅐␣-catenin complex have been thermodynamically and structurally defined. Conclusion:The architecture of ␣-catenin enables regulation of its interactions in the adhesive complex. Significance: The data provide molecular insights into the regulation of the cadherin⅐catenin complex.

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Section: Protein Constructsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Domain (Abd)mentioning

confidence: 99%

See 1 more Smart Citation

Structural and Thermodynamic Characterization of Cadherin·β-Catenin·α-Catenin Complex Formation

Pokutta

Choi

Ahlsén

et al. 2014

Journal of Biological Chemistry

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“…The view that a-catenin plays a key role within the CCC is reinforced by evidence that a-catenin behaves as a mechanosensor (Barry et al, 2014;le Duc et al, 2010;Yonemura et al, 2010), where actomyosin-force-generated tension leads to unfolding of an auto-inhibited middle (M)-region that allows binding to the a-catenin and F-actin-binding protein vinculin (Choi et al, 2012;Ishiyama et al, 2013;le Duc et al, 2010;Rangarajan and Izard, 2013;Yao et al, 2014;Yonemura et al, 2010). Evidence that the M-domain can bind to a number of F-actin-binding proteins (e.g.…”

Section: Introductionmentioning

confidence: 98%

α-catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism

Escobar

Desai

Ishiyama

et al. 2015

Journal of Cell Science

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The cadherin-catenin adhesion complex is a key contributor to epithelial tissue stability and dynamic cell movements during development and tissue renewal. How this complex is regulated to accomplish these functions is not fully understood. We identified several phosphorylation sites in mammalian aE-catenin (also known as catenin a-1) and Drosophila a-Catenin within a flexible linker located between the middle (M)-region and the carboxy-terminal actin-binding domain. We show that this phospho-linker (P-linker) is the main phosphorylated region of a-catenin in cells and is sequentially modified at casein kinase 2 and 1 consensus sites. In Drosophila, the P-linker is required for normal a-catenin function during development and collective cell migration, although no obvious defects were found in cadherin-catenin complex assembly or adherens junction formation. In mammalian cells, nonphosphorylatable forms of a-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of a-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the a-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.

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“…However, because actin filament/cadherin-catenin complex association is crucial for force transmission at AJs within epithelial sheets, there should be an unknown regulatory mechanism of actin-binding ability of α-catenin in the complex. Although crystal structure of the actin-binding domain of αN-catenin was determined (59), there is no model explaining the regulatory mechanism so far.…”

Section: The Journal Of Medical Investigation Vol 64 February 2017mentioning

confidence: 99%

Actin filament association at adherens junctions

Yonemura

2017

J. Med. Invest.

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: The adherens junction (AJ) is a cadherin-based and actin filament associated cell-to-cell junction. AJs can contribute to tissue morphogenesis and homeostasis and their association with actin filaments is crucial for the functions. There are three types of AJs in terms of the mode of actin filament/AJ association. Among many actin-binding proteins associated with AJs, α-catenin is one of the most important actin filament/AJ linkers that functions in all types of AJs. Although α-catenin in cadherin-catenin complex appears to bind to actin filaments within cells, it fails to bind to actin filaments in vitro mysteriously. Recent report revealed that α-catenin in the complex can bind to actin filaments in vitro when forces are applied to the filament. In addition to force-sensitive vinculin binding, α-catenin has another force-sensitive property of actin filament-binding. Elucidation of its significance and the molecular mechanism is indispensable for understanding AJ formation and maintenance during tissue morphogenesis, function and repair.

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An Autoinhibited Structure of α-Catenin and Its Implications for Vinculin Recruitment to Adherens Junctions

Cited by 111 publications

References 67 publications

Structural and Thermodynamic Characterization of Cadherin·β-Catenin·α-Catenin Complex Formation

Structural and Thermodynamic Characterization of Cadherin·β-Catenin·α-Catenin Complex Formation

α-catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism

Actin filament association at adherens junctions

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