title: Dynactin, a conserved, ubiquitously expressed component of an activator of vesicle motility mediated by cytoplasmic dynein.
abstract: Although cytoplasmic dynein is known to attach to microtubules and translocate toward their minus ends, dynein's ability to serve in vitro as a minus end-directed transporter of membranous organelles depends on additional soluble factors. We show here that a approximately 20S polypeptide complex (referred to as Activator I; Schroer, T. A., and M.P. Sheetz. 1991a. J. Cell Biol. 115:1309-1318.) stimulates dynein-mediated vesicle transport. A major component of the activator complex is a doublet of 150-kD polypeptides for which we propose the name dynactin (for dynein activator). The 20S dynactin complex is required for in vitro vesicle motility since depletion of it with a mAb to dynactin eliminates vesicle movement. Cloning of a brain specific isoform of dynactin from chicken reveals a 1,053 amino acid polypeptide composed of two coiled-coil alpha-helical domains interrupted by a spacer. Both this structural motif and the underlying primary sequence are highly conserved in vertebrates with 85% sequence identity within a central 1,000-residue domain of the chicken and rat proteins. As abundant as dynein, dynactin is ubiquitously expressed and appears to be encoded by a single gene that yields at least three alternative isoforms. The probable homologue in Drosophila is the gene Glued, whose protein product shares 50% sequence identity with vertebrate dynactin and whose function is essential for viability of most (and perhaps all) cells in the organism.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: S R
authors.initials: SR
authors.lastname: Gill
authors.forename: T A
authors.initials: TA
authors.lastname: Schroer
authors.forename: I
authors.initials: I
authors.lastname: Szilak
authors.forename: E R
authors.initials: ER
authors.lastname: Steuer
authors.forename: M P
authors.initials: MP
authors.lastname: Sheetz
authors.forename: D W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002478:Cells, Cultured; D002642:Chick Embryo; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA; D000072159:Dynactin Complex; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D015698:Genomic Library; D005967:Glue Proteins, Drosophila / Q000235:genetics; D007399:Interphase; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins; D008938:Mitosis; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D000072159:Dynactin Complex; D005967:Glue Proteins, Drosophila; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D004247:DNA; D004398:Dyneins