Faculty of 1000 evaluation for Deconstructing the cadherin-catenin-actin complex (original) (raw)
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Cell adhesion. The minimal cadherin-catenin complex binds to actin filaments under force
Science (New York, N.Y.), 2014
Linkage between the adherens junction (AJ) and the actin cytoskeleton is required for tissue development and homeostasis. In vivo findings indicated that the AJ proteins E-cadherin, β-catenin, and the filamentous (F)-actin binding protein αE-catenin form a minimal cadherin-catenin complex that binds directly to F-actin. Biochemical studies challenged this model because the purified cadherin-catenin complex does not bind F-actin in solution. Here, we reconciled this difference. Using an optical trap-based assay, we showed that the minimal cadherin-catenin complex formed stable bonds with an actin filament under force. Bond dissociation kinetics can be explained by a catch-bond model in which force shifts the bond from a weakly to a strongly bound state. These results may explain how the cadherin-catenin complex transduces mechanical forces at cell-cell junctions.
αE-catenin regulates actin dynamics independently of cadherin-mediated cell–cell adhesion
Journal of Cell Biology, 2010
αE-catenin binds the cell–cell adhesion complex of E-cadherin and β-catenin (β-cat) and regulates filamentous actin (F-actin) dynamics. In vitro, binding of αE-catenin to the E-cadherin–β-cat complex lowers αE-catenin affinity for F-actin, and αE-catenin alone can bind F-actin and inhibit Arp2/3 complex–mediated actin polymerization. In cells, to test whether αE-catenin regulates actin dynamics independently of the cadherin complex, the cytosolic αE-catenin pool was sequestered to mitochondria without affecting overall levels of αE-catenin or the cadherin–catenin complex. Sequestering cytosolic αE-catenin to mitochondria alters lamellipodia architecture and increases membrane dynamics and cell migration without affecting cell–cell adhesion. In contrast, sequestration of cytosolic αE-catenin to the plasma membrane reduces membrane dynamics. These results demonstrate that the cytosolic pool of αE-catenin regulates actin dynamics independently of cell–cell adhesion.
The Journal of cell biology, 1996
Epithelial cell-cell adhesion requires interactions between opposing extracellular domains of E-cadherin, and among the cytoplasmic domain of E-cadherin, catenins, and actin cytoskeleton. Little is known about how the cadherin-catenin-actin complex is assembled upon cell-cell contact, or how these complexes initiate and strengthen adhesion. We have used time-lapse differential interference contrast (DIC) imaging to observe the development of cell-cell contacts, and quantitative retrospective immunocytochemistry to measure recruitment of proteins to those contacts. We show that E-cadherin, alpha-catenin, and beta-catenin, but not plakoglobin, coassemble into Triton X-100 insoluble (TX-insoluble) structures at cell-cell contacts with kinetics similar to those for strengthening of E-cadherin-mediated cell adhesion (Angres, B., A. Barth, and W.J. Nelson. 1996. J. Cell Biol. 134:549-557). TX-insoluble E-cadherin, alpha-catenin, and beta-catenin colocalize along cell-cell contacts in spat...
Monomeric Alpha-catenin links cadherin to the actin cytoskeleton
The linkage of adherens junctions to the actin cytoskeleton is essential for cell adhesion. The contribution of the cadherincatenin complex to the interaction between actin and the adherens junction remains an intensely investigated subject that centres on the function of -catenin, which binds to cadherin through -catenin and can bind F-actin directly or indirectly. Here, we delineate regions within Drosophila -Catenin ( -Cat) that are important for adherens junction performance in static epithelia and dynamic morphogenetic processes. Moreover, we address whether persistent -catenin-mediated physical linkage between cadherin and F-actin is crucial for cell adhesion and characterize the functions of -catenin monomers and dimers at adherens junctions. Our data support the view that monomeric -catenin acts as an essential physical linker between the cadherin -catenin complex and the actin cytoskeleton, whereas -catenin dimers are cytoplasmic and form an equilibrium with monomeric junctional -catenin.
Cell, 2005
Epithelial cell-cell junctions, organized by adhesion proteins and the underlying actin cytoskeleton, are considered to be stable structures maintaining the structural integrity of tissues. Contrary to the idea that a-catenin links the adhesion protein Ecadherin through b-catenin to the actin cytoskeleton, in the accompanying paper we report that a-catenin does not bind simultaneously to both E-cadherin-b-catenin and actin filaments. Here we demonstrate that a-catenin exists as a monomer or a homodimer with different binding properties. Monomeric a-catenin binds more strongly to E-cadherin-b-catenin, whereas the dimer preferentially binds actin filaments. Different molecular conformations are associated with these different binding states, indicating that a-catenin is an allosteric protein. Significantly, a-catenin directly regulates actin-filament organization by suppressing Arp2/3-mediated actin polymerization, likely by competing with the Arp2/3 complex for binding to actin filaments. These results indicate a new role for a-catenin in local regulation of actin assembly and organization at sites of cadherin-mediated cell-cell adhesion.
α-Catenin-mediated cadherin clustering couples cadherin and actin dynamics
The Journal of cell biology, 2015
The function of the actin-binding domain of α-catenin, αABD, including its possible role in the direct anchorage of the cadherin-catenin complex to the actin cytoskeleton, has remained uncertain. We identified two point mutations on the αABD surface that interfere with αABD binding to actin and used them to probe the role of α-catenin-actin interactions in adherens junctions. We found that the junctions directly bound to actin via αABD were more dynamic than the junctions bound to actin indirectly through vinculin and that recombinant αABD interacted with cortical actin but not with actin bundles. This interaction resulted in the formation of numerous short-lived cortex-bound αABD clusters. Our data suggest that αABD clustering drives the continuous assembly of transient, actin-associated cadherin-catenin clusters whose disassembly is maintained by actin depolymerization. It appears then that such actin-dependent αABD clustering is a unique molecular mechanism mediating both integri...
Functional Domains of alpha -Catenin Required for the Strong State of Cadherin-based Cell Adhesion
The Journal of Cell Biology, 1999
The interaction of cadherin–catenin complex with the actin-based cytoskeleton through α-catenin is indispensable for cadherin-based cell adhesion activity. We reported previously that E-cadherin–α-catenin fusion molecules showed cell adhesion and cytoskeleton binding activities when expressed in nonepithelial L cells. Here, we constructed deletion mutants of E-cadherin–α-catenin fusion molecules lacking various domains of α-catenin and introduced them into L cells. Detailed analysis identified three distinct functional domains of α-catenin: a vinculin/α-actinin-binding domain, a ZO-1-binding domain, and an adhesion-modulation domain. Furthermore, cell dissociation assay revealed that the fusion molecules containing the ZO-1-binding domain in addition to the adhesion-modulation domain conferred the strong state of cell adhesion activity on transfectants, although those lacking the ZO-1-binding domain conferred only the weak state. The disorganization of actin-based cytoskeleton by cy...
Functional Domains of α-Catenin Required for the Strong State of Cadherin-based Cell Adhesion
The Journal of Cell Biology, 1999
The interaction of cadherin–catenin complex with the actin-based cytoskeleton through α-catenin is indispensable for cadherin-based cell adhesion activity. We reported previously that E-cadherin–α-catenin fusion molecules showed cell adhesion and cytoskeleton binding activities when expressed in nonepithelial L cells. Here, we constructed deletion mutants of E-cadherin–α-catenin fusion molecules lacking various domains of α-catenin and introduced them into L cells. Detailed analysis identified three distinct functional domains of α-catenin: a vinculin/α-actinin-binding domain, a ZO-1-binding domain, and an adhesion-modulation domain. Furthermore, cell dissociation assay revealed that the fusion molecules containing the ZO-1-binding domain in addition to the adhesion-modulation domain conferred the strong state of cell adhesion activity on transfectants, although those lacking the ZO-1-binding domain conferred only the weak state. The disorganization of actin-based cytoskeleton by cy...