title: An autoinhibited structure of α-catenin and its implications for vinculin recruitment to adherens junctions.
abstract: α-Catenin is an actin- and vinculin-binding protein that regulates cell-cell adhesion by interacting with cadherin adhesion receptors through β-catenin, but the mechanisms by which it anchors the cadherin-catenin complex to the actin cytoskeleton at adherens junctions remain unclear. Here we determined crystal structures of αE-catenin in the autoinhibited state and the actin-binding domain of αN-catenin. Together with the small-angle x-ray scattering analysis of full-length αN-catenin, we deduced an elongated multidomain assembly of monomeric α-catenin that structurally and functionally couples the vinculin- and actin-binding mechanisms. Cellular and biochemical studies of αE- and αN-catenins show that αE-catenin recruits vinculin to adherens junctions more effectively than αN-catenin, partly because of its higher affinity for actin filaments. We propose a molecular switch mechanism involving multistate conformational changes of α-catenin. This would be driven by actomyosin-generated tension to dynamically regulate the vinculin-assisted linkage between adherens junctions and the actin cytoskeleton.
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ishiyama
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Tanaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Abe
authors.forename: Yoo Jeong
authors.initials: YJ
authors.lastname: Yang
authors.forename: Yazan M
authors.initials: YM
authors.lastname: Abbas
authors.forename: Masataka
authors.initials: M
authors.lastname: Umitsu
authors.forename: Bhushan
authors.initials: B
authors.lastname: Nagar
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Bueler
authors.forename: John L
authors.initials: JL
authors.lastname: Rubinstein
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeichi
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Ikura
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D022005:Adherens Junctions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D016596:Vinculin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051178:alpha Catenin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C495272:Ctnna1 protein, mouse; C486820:Ctnna2 protein, mouse; D009419:Nerve Tissue Proteins; D051178:alpha Catenin; D016596:Vinculin
keywords: Adherens Junction; Cadherins; Catenin; Cell Adhesion; Cytoskeleton; Vinculin; α-Catenin