Dynamic visualization of a-Catenin reveals rapid, reversible conformation switching between tension states
- Dynamic visualization of a-Catenin reveals rapid, reversible conformation switching between tension states
- 김태진; Shuai Zheng; Jie Sun; Ismaeel Muhamed; Jun Wu; Lei Lei; Xinyu Kong; Deborah E Leckband; Yingxiao Wang
- FRET; catenin; Visualization; Force
- Issue Date
- Current biology : CB
- VOL 25, NO 2, 218-224
- The cytosolic protein alpha-catenin is a postulated force transducer at cadherin complexes . The demonstration of force activation, identification of consequent downstream events in live cells, and development of tools to study these dynamic processes in living cells are central to elucidating the role of alpha-catenin in cellular mechanics and tissue function [2-10]. Here we demonstrate that alpha-catenin is a force-activatable mechanotransducer at cell-cell junctions by using an engineered alpha-catenin conformation sensor based on fluorescence resonance energy transfer (FRET). This sensor reconstitutes alpha-catenin-dependent functions in alpha-catenin-depleted cells and recapitulates the behavior of the endogenous protein. Dynamic imaging of cells expressing the sensor demonstrated that alpha-catenin undergoes immediate, reversible conformation switching in direct response to different mechanical perturbations of cadherin adhesions. Combined magnetic twisting cytometry with dynamic FRET imaging  revealed rapid, local conformation switching upon the mechanical stimulation of specific cadherin bonds. At acutely stretched cell-cell junctions, the immediate, reversible conformation change further reveals that alpha-catenin behaves like an elastic spring in series with cadherin and actin. The force-dependent recruitment of vinculin-a principal alpha-catenin effector-to junctions requires the vinculin binding site of the alpha-catenin sensor [1, 12-16]. In cells, the relative rates of force-dependent alpha-catenin conformation switching and vinculin recruitment reveal that alpha-catenin activation and vinculin recruitment occur sequentially, rather than in a concerted process, with vinculin accumulation being significantly slower. This engineered alpha-catenin sensor revealed that alpha-catenin is a reversible, stretch-activatable sensor that mechanically links cadherin complexes and actin and is an indispensabl
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.