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Until recently, dynein was the least understood of the cytoskeletal motors. However, a wealth of new structural, mechanistic, and cell biological data is shedding light on how this complicated minus-end-directed, microtubule-based motor works. Cytoplasmic dynein-1 performs a wide array of functions in most eukaryotes, both in interphase, in which it transports organelles, proteins, mRNAs, and viruses, and in mitosis and meiosis. Mutations in dynein or its regulators are linked to neurodevelopmental and neurodegenerative diseases. Here, we begin by providing a synthesis of recent data to describe the current model of dynein's mechanochemical cycle. Next, we discuss regulators of dynein, with particular focus on those that directly interact with the motor to modulate its recruitment to microtubules, initiate cargo transport, or activate minus-end-directed motility.
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Supplemental Video 1: Dynein’s mechanochemical cycle. This video shows an animated version of dynein’s mechanochemical cycle, as outlined in Figure 1d. The video illustrates a single step for a dynein head. In contrast to Figure 1d, here we include a full dimer. The color coding is the same as that used in Figure 1. We use steps to describe dynein’s mechanochemical cycle in the main text and to illustrate it in Figure 1d. We indicate those steps in this Supplemental Video so the reader can refer to the main text for a full description of the changes that take place.