Competition between motor molecules (kinesin and cytoplasmic dynein) and fibrous microtubule-associated proteins in binding to microtubules.
In neuronal cells, microtubule-associated proteins (MAPs) can be classified into two distinct groups. One consists of force-producing MAPs, the main components of which are kinesin and cytoplasmic dynein. The other is composed of fibrous MAPs, which include tau and MAP2. Many studies have been performed on the respective groups to understand their structures and functions. However, the problem of how the groups interact with each other on microtubules is still unresolved. To elucidate the interaction between kinesin or cytoplasmic dynein and tau or MAP2, we performed three experiments: competition, motility assay, and cosedimentation. To distinguish whether the binding competition is caused by steric hindrance of the projection domains of MAPs or by the competition of the binding sites on microtubules, we used microtubule binding domains of tau and MAP2 as well as native proteins. Our results revealed that kinesin or cytoplasmic dynein and tau or MAP2 complete for almost the same binding domains located on the carboxyl-terminal side of alpha- and the amino-terminal side of beta-tubulin from the site of subtilisin cleavage. Furthermore, the projection of tau, and probably of MAP2, might inhibit the binding of kinesin or cytoplasmic dynein to microtubules by steric hindrance. These findings will provide a useful step toward understanding the regulation system of intracellular organelle transport.
Hagiwara
H
H
Department of Anatomy and Cell Biology, School of Medicine, University of Tokyo, Japan.
Yorifuji
H
H
Sato-Yoshitake
R
R
Hirokawa
N
N
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000302:isolation & purification / Q000378:metabolism*; D016547:Kinesins / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008961:Models, Structural; D011485:Protein Binding; D013552:Swine; D014404:Tubulin / Q000302:isolation & purification / Q000378:metabolism; D014461:Ultracentrifugation; D016875:tau Proteins / Q000302:isolation & purification / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D014404:Tubulin; D016875:tau Proteins; D004398:Dyneins; D016547:Kinesins