Mechanics of Cytoplasmic Dynein

Cytoplasmic dynein is responsible for motility and force generation functions towards the microtubule minus end. In comparison to kinesin and myosin motors, the mechanism of dynein motility was not well understood due to the complexity of its structure and massive size. Using single-molecule imaging methods, we presented a robust mechanistic model of how dynein steps along microtubules and generates force. We reversed the direction of dynein motility by protein engineering, which explained why all dyneins move towards the microtubule minus-end. We have also studied the activation and motility of mammalian dynein-dynactin complexes, and how the dynein transport machinery is regulated by dynein-associated factors, microtubule-associated proteins, and cargo adaptors. These results alter our view on how dynein functions as a motor and transports cargos in cells.