Differential regulation of dynein and kinesin motor proteins by tau.
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.
Dixit
Ram
R
Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ross
Jennifer L
JL
Goldman
Yale E
YE
Holzbaur
Erika L F
EL
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D016875:tau Proteins; D004398:Dyneins; D016547:Kinesins