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
김태진Shuai ZhengJie SunIsmaeel MuhamedJun WuLei LeiXinyu KongDeborah E LeckbandYingxiao 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 [1]. 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 [11] 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
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