Evidence for cooperative interactions between the two motor domains of cytoplasmic dynein.
Cytoplasmic dynein is a force-transducing ATPase that powers the movement of cellular cargoes along microtubules. Two identical heavy chain polypeptides (> 500 kDa) of the cytoplasmic dynein complex contain motor domains that possess the ATPase and microtubule-binding activities required for force production [1]. It is of great interest to determine whether both heavy chains (DHCs) in the dynein complex are required for progression of the mechanochemical cycle and motility, as observed for other dimeric motors. We have used transgenic constructs to investigate cooperative interactions between the two motor domains of the Drosophila cytoplasmic dynein complex. We show that 138 kDa and 180 kDa amino-terminal fragments of DHC can assemble with full-length DHC to form heterodimeric complexes containing only a single motor domain. The single-headed dynein complexes can bind and hydrolyze ATP, yet do not show the ATP-induced detachment from microtubules that is characteristic of wild-type homodimeric dynein. These results suggest that cooperative interactions between the monomeric units of the dimer are required for efficient ATP-induced detachment of dynein and unidirectional movement along the microtubule.
Department of Genetics, Cell Biology and Development, University of Minnesota, St Paul, Minnesota 55108, USA.
S J
SJ
Iyadurai
M G
MG
Li
S P
SP
Gilbert
T S
TS
Hays
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D003593:Cytoplasm / Q000201:enzymology*; D004330:Drosophila; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D000939:Epitopes / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D017239:Paclitaxel / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
D000939:Epitopes; D010455:Peptides; D000255:Adenosine Triphosphate; D004398:Dyneins; D017239:Paclitaxel