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) the cell body along microtubules. Previous studies have provided compelling evidence that conventional kinesin is a major motor for anterograde fast axonal transport. It is reasonable to expect that cytoplasmic dynein is a fast retrograde motor, but relatively few tests of dynein function have been reported with neurons of intact organisms. In extruded axoplasm, antibody disruption of kinesin or the dynactin complex (a dynein activator) inhibits both retrograde and anterograde transport. We have tested the functions of the cytoplasmic dynein heavy chain (cDhc64C) and the p150(Glued) (Glued) component of the dynactin complex with the use of genetic techniques in Drosophila. cDhc64C and Glued mutations disrupt fast organelle transport in both directions. The mutant phenotypes, larval posterior paralysis and axonal swellings filled with retrograde and anterograde cargoes, were similar to those caused by kinesin mutations. Why do specific disruptions of unidirectional motor systems cause bidirectional defects? Direct protein interactions of kinesin with dynein heavy chain and p150(Glued) were not detected. However, strong dominant genetic interactions between kinesin, dynein, and dynactin complex mutations in axonal transport were observed. The genetic interactions between kinesin and either Glued or cDhc64C mutations were stronger than those between Glued and cDhc64C mutations themselves. The shared bidirectional disruption phenotypes and the dominant genetic interactions demonstrate that cytoplasmic dynein, the dynactin complex, and conventional kinesin are interdependent in fast axonal transport.
Martin
M
M
Department of Biology, Indiana University, Bloomington, Indiana 47405-6801, USA.
Iyadurai
S J
SJ
Gassman
A
A
Gindhart
J G
JG
Hays
T S
TS
Saxton
W M
WM
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000235:genetics* / Q000378:metabolism; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018715:Microscopy, Video; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D011233:Precipitin Tests
D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D004398:Dyneins; D016547:Kinesins