title: Differential regulation of dynein and kinesin motor proteins by tau.
abstract: 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.
authors.affiliation: Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Dixit
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Ross
authors.forename: Yale E
authors.initials: YE
authors.lastname: Goldman
authors.forename: Erika L F
authors.initials: EL
authors.lastname: Holzbaur
mesh_terms: 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*
chemical_list: D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D016875:tau Proteins; D004398:Dyneins; D016547:Kinesins