title: Autoinhibition and cooperative activation mechanisms of cytoplasmic dynein.
abstract: Cytoplasmic dynein is a two-headed microtubule-based motor responsible for diverse intracellular movements, including minus-end-directed transport of organelles. The motility of cargo transporters is regulated according to the presence or absence of cargo; however, it remains unclear how cytoplasmic dynein achieves such regulation. Here, using a recombinant and native dynein complex in vitro, we show that lone, single dynein molecules are in an autoinhibited state, in which the two motor heads are stacked together. In this state, dynein moves diffusively along a microtubule with only a small bias towards the minus end of the microtubule. When the two heads were physically separated by a rigid rod, the movement of dynein molecules became directed and processive. Furthermore, assembly of multiple dynein molecules on a single cargo enabled them to move unidirectionally and generate force cooperatively. We thus propose a mechanism of autonomous on-off switching of cargo transport, in which single dynein molecules in the cell are autoinhibited through intramolecular head-head stacking and become active when they assemble as a team on a cargo.
authors.affiliation: 1] Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan [2] Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe, Hyogo 651-2492, Japan [3] CREST, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0076, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Torisawa
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Ichikawa
authors.affiliation: Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe, Hyogo 651-2492, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Furuta
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Saito
authors.affiliation: 1] Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe, Hyogo 651-2492, Japan [2] CREST, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0076, Japan [3] Graduate School of Life Science, University of Hyogo, Harima Science Park City, Hyogo 678-1297, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Oiwa
authors.affiliation: Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe, Hyogo 651-2492, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kojima
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Yoko Y
authors.initials: YY
authors.lastname: Toyoshima
authors.affiliation: Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe, Hyogo 651-2492, Japan.
authors.forename: Ken'ya
authors.initials: K
authors.lastname: Furuta
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D056445:Cytoplasmic Dyneins