Cytoplasmic dynein, the dynactin complex, and kinesin are interdependent and essential for fast axonal transport

In axons, organelles move away from (anterograde) and toward (retrograde) t he cell body along microtubules. Previous studies have provided compelling evidence that conventional kinesin is a major motor for anterograde fast ax onal transport. It is reasonable to expect that cytoplasmic dynein is a fas t retrograde motor, but relatively few tests of dynein function have been r eported with neurons of intact organisms. In extruded axoplasm, antibody di sruption of kinesin or the dynactin complex (a dynein activator) inhibits b oth retrograde and anterograde transport. We have tested the functions of t he cytoplasmic dynein heavy chain (cDhc64C) and the p150(Glued) (Glued) com ponent of the dynactin complex with the use of genetic techniques in Drosop hila. cDhc64C and Glued mutations disrupt fast organelle transport in both directions. The mutant phenotypes, larval posterior paralysis and axonal sw ellings filled with retrograde and anterograde cargoes, were similar to tho se caused by kinesin mutations. Why do specific disruptions of unidirection al motor systems cause bidirectional. defects? Direct protein interactions of kinesin with dynein heavy chain and p150(Glued) were not detected. Howev er, strong dominant genetic interactions between kinesin, dynein, and dynac tin complex mutations in axonal transport were observed. The genetic intera ctions between kinesin and either Glued or cDhc64C mutations were stronger than those between Glued and cDhc64C mutations themselves. The shared bidir ectional disruption phenotypes and the dominant genetic interactions demons trate that cytoplasmic dynein, the dynactin complex, and conventional kines in are interdependent in fast axonal transport.