Practice question

Intracellular transport operates through antagonistic plus-end kinesins and minus-end dynein along same microtubule tracks. Under normal conditions kinesin-1 and kinesin-3 carry cargo outward toward cell periphery, dynein-dynactin returns cargo toward centrosome where microtubule minus ends converge. Acute inhibition by overexpression of dynamitin CC1 fragment dissociating dynactin, treatment with ciliobrevin D blocking AAA1 ATPase, or inducible degron of dynein heavy chain abolishes retrograde motion while anterograde motion persists. Consequences include dispersion of Golgi, accumulation of endosomes and lysosomes at tips of processes, impaired autophagosome-lysosome fusion and increased peripheral residence of signaling endosomes. Microtubules remain polymerized because dynein inhibition does not alter tubulin GTP cap dynamics. Actin compensates only for short-range delivery via myosin V, insufficient for long-range concentration. Consequently phenotype is peripheral clustering rather than enhanced centripetal movement, illustrating tug-of-war principle governing organelle positioning and balance of opposing motors. Integration with cell cycle kinases, calcium signaling and mechanical cues ensures coordinated remodeling during growth, migration and differentiation.