30
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      ZW10 Helps Recruit Dynactin and Dynein to the Kinetochore

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mutations in the Drosophila melanogaster zw10 gene, which encodes a conserved, essential kinetochore component, abolish the ability of dynein to localize to kinetochores. Several similarities between the behavior of ZW10 protein and dynein further support a role for ZW10 in the recruitment of dynein to the kinetochore: ( a) in response to bipolar tension across the chromosomes, both proteins mostly leave the kinetochore at metaphase, when their association with the spindle becomes apparent; ( b) ZW10 and dynein both bind to functional neocentromeres of structurally acentric minichromosomes; and ( c) the localization of both ZW10 and dynein to the kinetochore is abolished in cells mutant for the gene rough deal. ZW10's role in the recruitment of dynein to the kinetochore is likely to be reasonably direct, because dynamitin, the p50 subunit of the dynactin complex, interacts with ZW10 in a yeast two-hybrid screen. Since in zw10 mutants no defects in chromosome behavior are observed before anaphase onset, our results suggest that dynein at the kinetochore is essential for neither microtubule capture nor congression to the metaphase plate. Instead, dynein's role at the kinetochore is more likely to be involved in the coordination of chromosome separation and/or poleward movement at anaphase onset.

          Related collections

          Most cited references51

          • Record: found
          • Abstract: found
          • Article: not found

          Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts.

          Functional nuclei and mitotic spindles are shown to assemble around DNA-coated beads incubated in Xenopus egg extracts. Bipolar spindles assemble in the absence of centrosomes and kinetochores, indicating that bipolarity is an intrinsic property of microtubules assembling around chromatin in a mitotic cytoplasm. Microtubules nucleated at dispersed sites with random polarity rearrange into two arrays of uniform polarity. Spindle-pole formation requires cytoplasmic dynein-dependent translocation of microtubules across one another. It is proposed that spindles form in the absence of centrosomes by motor-dependent sorting of microtubules according to their polarity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A complex of NuMA and cytoplasmic dynein is essential for mitotic spindle assembly.

            NuMA is a nuclear protein during interphase but redistributes to the spindle poles early in mitosis. To investigate its role during spindle formation, we tested spindle assembly in frog egg extracts from which NuMA was immunodepleted. Immunodepletion revealed that NuMA forms a complex with cytoplasmic dynein and dynactin. The depleted extracts failed to assemble normal mitotic spindles, producing, instead, chromatin-associated irregular arrays of microtubules lacking characteristic spindle poles. A subdomain of the NuMA tail was shown to induce microtubule aster formation by mediating microtubule bundling. Our findings suggest that NuMA forms bifunctional complexes with cytoplasmic dynein and dynactin that can tether microtubules at the spindle poles and that are essential for mitotic spindle pole assembly and stabilization.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis

              Dynactin is a multi-subunit complex which has been implicated in cytoplasmic dynein function, though its mechanism of action is unknown. In this study, we have characterized the 50-kD subunit of dynactin, and analyzed the effects of its overexpression on mitosis in living cells. Rat and human cDNA clones revealed p50 to be novel and highly conserved, containing three predicted coiled-coil domains. Immunofluorescence staining of dynactin and cytoplasmic dynein components in cultured vertebrate cells showed that both complexes are recruited to kinetochores during prometaphase, and concentrate near spindle poles thereafter. Overexpression of p50 in COS-7 cells disrupted mitosis, causing cells to accumulate in a prometaphase-like state. Chromosomes were condensed but unaligned, and spindles, while still bipolar, were dramatically distorted. Sedimentation analysis revealed the dynactin complex to be dissociated in the transfected cultures. Furthermore, both dynactin and cytoplasmic dynein staining at prometaphase kinetochores was markedly diminished in cells expressing high levels of p50. These findings represent clear evidence for dynactin and cytoplasmic dynein codistribution within cells, and for the presence of dynactin at kinetochores. The data also provide direct in vivo evidence for a role for vertebrate dynactin in modulating cytoplasmic dynein binding to an organelle, and implicate both dynactin and dynein in chromosome alignment and spindle organization.
                Bookmark

                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                10 August 1998
                : 142
                : 3
                : 763-774
                Affiliations
                [* ]Section of Genetics and Development, Cornell University, Ithaca, New York 14853-2703; and []Departments of Genetics and Cell Biology, University of Minnesota, St. Paul, Minnesota 55108
                Author notes

                Address all correspondence to Michael L. Goldberg, Section of Genetics and Development, Cornell University, Ithaca, NY 14853-2703. Tel.: (607) 254-4802. Fax: (607) 255-6249. E-mail: mlg11@ 123456cornell.edu

                Article
                10.1083/jcb.142.3.763
                2148168
                9700164
                638e8a22-a17a-4449-ba81-41638dd93040
                Copyright @ 1998
                History
                : 14 April 1998
                : 1 July 1998
                Categories
                Regular Articles

                Cell biology
                zw10,dynein,dynamitin,rough deal,kinetochore
                Cell biology
                zw10, dynein, dynamitin, rough deal, kinetochore

                Comments

                Comment on this article