Biochemical and structural analysis of alpha-catenin in cell-cell contacts.
Cadherins are transmembrane adhesion molecules that mediate homotypic cell-cell contact. In adherens junctions, the cytoplasmic domain of cadherins is functionally linked to the actin cytoskeleton through a series of proteins known as catenins. E-cadherin binds to beta-catenin, which in turn binds to alpha-catenin to form a ternary complex. alpha-Catenin also binds to actin, and it was assumed previously that alpha-catenin links the cadherin-catenin complex to actin. However, biochemical, structural and live-cell imaging studies of the cadherin-catenin complex and its interaction with actin show that binding of beta-catenin to alpha-catenin prevents the latter from binding to actin. Biochemical and structural data indicate that alpha-catenin acts as an allosteric protein whose conformation and activity changes depending on whether or not it is bound to beta-catenin. Initial contacts between cells occur on dynamic lamellipodia formed by polymerization of branched actin networks, a process controlled by the Arp2/3 (actin-related protein 2/3) complex. alpha-Catenin can suppress the activity of Arp2/3 by competing for actin filaments. These findings lead to a model for adherens junction formation in which clustering of the cadherin-beta-catenin complex recruits high levels of alpha-catenin that can suppress the Arp2/3 complex, leading to cessation of lamellipodial movement and formation of a stable contact. Thus alpha-catenin appears to play a central role in cell-cell contact formation.
Pokutta
Sabine
S
Department of Structural Biology, D100 Fairchild Science Building, Stanford University School of Medicine, Stanford, CA 94305-5126, U.S.A.
Drees
Frauke
F
Yamada
Soichiro
S
Nelson
W James
WJ
Weis
William I
WI
D051376:Actin-Related Protein 2-3 Complex / Q000737:chemistry / Q000502:physiology; D000199:Actins / Q000737:chemistry / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D003599:Cytoskeleton / Q000737:chemistry / Q000502:physiology; D008954:Models, Biological; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051178:alpha Catenin / Q000737:chemistry* / Q000502:physiology*; D051176:beta Catenin / Q000737:chemistry / Q000502:physiology
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D015820:Cadherins; D051178:alpha Catenin; D051176:beta Catenin