| Speaker: |
Noboru Ishiyama
Ontario Cancer Institute, Canada |
| Title: |
Coping with stress: Dynamic structural changes in α-catenin regulate the cadherin-actin linkage |
| Summary : | ƒ¿-catenin is an actin-binding protein responsible for connecting the cadherin-catenin complex to the actin cytoskeleton at adherens junctions. However, the mechanisms by which it maintains the cadherin-actin linkage at intercellular junctions under mechanical stress remain unclear. To better understand how ƒ¿-catenin functions at this critical interface, we have recently determined crystal structures of ƒ¿E-catenin in the autoinhibited state and the actin-binding domain of ƒ¿N-catenin. Together with the small-angle X-ray scattering analysis of full-length ƒ¿N-catenin, we deduced an elongated multidomain assembly of monomeric ƒ¿-catenin that structurally and functionally couples the vinculin- and actin-binding mechanisms. Cellular and biochemical studies of ƒ¿E- and ƒ¿N-catenins show that ƒ¿E-catenin recruits vinculin, an F-actin-binding protein, to adherens junctions more effectively than ƒ¿N-catenin, partly owing to its higher affinity for actin filaments. We propose a molecular switch mechanism involving multi-state conformational changes of ƒ¿-catenin. This would be driven by actomyosin-generated tension to dynamically regulate the vinculin-assisted linkage between adherens junctions and the actin cytoskeleton. |
