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Category CDBセミナー
Date and Time 2014-06-10 16:00 - 17:00
Venue Seminar Room A7F
Speaker Noboru Ishiyama
Affiliation Ontario Cancer Institute, Canada
Title Coping with stress: Dynamic structural changes in α-catenin regulate the cadherin-actin linkage
Poster click here to download(PDF)
Host Shigenobu Yonemura
Summary α-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 α-catenin functions at this critical interface, we have recently 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, an F-actin-binding protein, to adherens junctions more effectively than αN-catenin, partly owing to its higher affinity for actin filaments. We propose a molecular switch mechanism involving multi-state 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.
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