Differential Regulation of Dynein and Kinesin Motor Proteins by Tau

American Association for the Advancement of Science (AAAS) - Tập 319 Số 5866 - Trang 1086-1089 - 2008
Ram Dixit1, Jennifer L. Ross1, Yale E. Goldman1, Erika L.F. Holzbaur1
1Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.

Tóm tắt

Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. Motor proteins thus encounter MAPs frequently along their path. To determine the effects of tau on dynein and kinesin motility, we conducted single-molecule studies of motor proteins moving along tau-decorated microtubules. Dynein tended to reverse direction, whereas kinesin tended to detach at patches of bound tau. Kinesin was inhibited at about a tenth of the tau concentration that inhibited dynein, and the microtubule-binding domain of tau was sufficient to inhibit motor activity. The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport.

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We thank E. Mandelkow for the tau constructs R. Kudaravalli for purified kinesin S. Shah for data analysis and M. Ostap and members of the Holzbaur and Goldman labs for helpful comments. This work was supported by NIH grants P01-AR-051174 to the Pennsylvania Muscle Institute and GM-48661 to E.L.F.H. and NSF grant NSEC DMR04-25780 to the Penn Nano/Bio Interface Center.