title: Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes.
abstract: Cytoplasmic dynein is a molecular motor that transports a large variety of cargoes (e.g., organelles, messenger RNAs, and viruses) along microtubules over long intracellular distances. The dynactin protein complex is important for dynein activity in vivo, but its precise role has been unclear. Here, we found that purified mammalian dynein did not move processively on microtubules in vitro. However, when dynein formed a complex with dynactin and one of four different cargo-specific adapter proteins, the motor became ultraprocessive, moving for distances similar to those of native cargoes in living cells. Thus, we propose that dynein is largely inactive in the cytoplasm and that a variety of adapter proteins activate processive motility by linking dynactin to dynein only when the motor is bound to its proper cargo.
authors.affiliation: Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: McKenney
authors.affiliation: Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Huynh
authors.affiliation: Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Marvin E
authors.initials: ME
authors.lastname: Tanenbaum
authors.affiliation: Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Gira
authors.initials: G
authors.lastname: Bhabha
authors.affiliation: Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. vale@ucsf.edu.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Vale
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D056445:Cytoplasmic Dyneins / Q000737:chemistry / Q000378:metabolism*; D000072159:Dynactin Complex; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism*; D009038:Motion; D021381:Protein Transport; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D056445:Cytoplasmic Dyneins