Motile Properties of Cytoplasmic Dynein

Cytoplasmic dynein is the major minus-end-directed microtubule-based motor in nearly all eukaryotic cells. Due to its large size and subunit complexity, dissecting the motile properties of dynein has been challenging. However, recent advances in recombinant approaches to purify dynein, as well as studies with the native motors, have begun to reveal the details of how dynein steps along microtubules and responds to externally applied loads. Compared to studies on the other cytoskeletal motors, myosin and kinesin, studies of dynein are still in their infancy, leading to a number of controversies regarding the dynein motile mechanism. However, a consensus is beginning to emerge from single-molecule studies that dynein is a highly processive motor, which can take forward, backward and diagonal steps related in size to the minimum repeat unit of the microtubule (8 nm). Here we discuss some of the more controversial aspects of the dynein stepping mechanism and response to load. We also review what is known about dynein regulation by its multiple ATP-binding sites and associated cofactors, the dynactin complex, LIS1, and NudE.