Practice question

Cytoplasmic dynein generates minus-end directed transport using a microtubule-binding domain at the tip of an antiparallel coiled-coil stalk that extends from the AAA ring. The binding interface undergoes ATP-dependent registry shift between strong and weak states. When mutations, deletion or antibody blockade abolishes microtubule attachment, the motor continues to bind ATP and hydrolyze it via AAA1, but force cannot be transmitted to the filament, uncoupling ATPase activity from movement. Cargo adaptors such as BICD2, HOOK and dynactin still recruit dynein via tail and intermediate chains, but vesicles including late endosomes, lysosomes, Golgi elements and messenger ribonucleoprotein granules remain stationary, while kinesin-mediated plus-end movement proceeds unopposed. This results in peripheral accumulation and loss of centripetal concentration near the microtubule-organizing center. The phenotype mimics genetic dynein loss, demonstrating that stable microtubule engagement is mandatory for productive power stroke rather than for ATP hydrolysis, separating chemical and mechanical cycles in mechanochemical coupling. Integration with cell cycle kinases, calcium signaling and mechanical cues ensures coordinated remodeling during growth, migration and differentiation.