Kinetochore Dynein Is Required for Chromosome Motion and Congression Independent of the Spindle Checkpoint
- 1 June 2007
- journal article
- other
- Published by Elsevier BV in Current Biology
- Vol. 17 (11), 973-980
- https://doi.org/10.1016/j.cub.2007.04.056
Abstract
During mitosis, the motor molecule cytoplasmic dynein plays key direct and indirect roles in organizing microtubules (MTs) into a functional spindle. At this time, dynein is also recruited to kinetochores, but its role or roles at these organelles remain vague, partly because inhibiting dynein globally disrupts spindle assembly [ 1 Echeverri C.J. Paschal B.M. Vaughan K.T. Valee R.B. Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis. J. Cell Biol. 1996; 132 : 617-633 Crossref PubMed Scopus (543) Google Scholar , 2 Purohit A. Tynan S.H. Vallee R.B. Doxsey S.J. Direct interaction of pericentirn with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization. J. Cell Biol. 1999; 147 : 481-491 Crossref PubMed Scopus (156) Google Scholar , 3 Gaetz J. Kapoor T.M. Dynein/dynactin regulates metaphase spindle length by targeting depolymerizing activities to spindle poles. J. Cell Biol. 2004; 166 : 465-471 Crossref PubMed Scopus (152) Google Scholar , 4 Maiato H. Khodjakov A. Rieder C.L. Drosophila CLASP is required for the incorporation of microtubule subunits into fluxing kinetochore fibers. Nat. Cell Biol. 2005; 7 : 42-47 Crossref PubMed Scopus (144) Google Scholar ]. However, dynein can be selectively depleted from kinetochores by disruption of ZW10 [ 5 Starr D.A. Williams B.C. Hays T.S. Goldberg M.L. ZW10 helps recruit dynactin and dynein to the kinetochore. J. Cell Biol. 1998; 142 : 763-774 Crossref PubMed Scopus (210) Google Scholar ], and recent studies with this approach conclude that kinetochore-associated dynein (KD) functions to silence the spindle-assembly checkpoint (SAC) [ 6 Karess R.E. Rod-Zw10-Zwilch: A key player in the spindle checkpoint. Trends Cell Biol. 2005; 15 : 386-392 Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar ]. Here we use dynein-antibody microinjection and the RNAi of ZW10 to explore the role of KD in chromosome behavior during mitosis in mammals. We find that depleting or inhibiting KD prevents the rapid poleward motion of attaching kinetochores but not kinetochore fiber (K fiber) formation. However, after kinetochores attach to the spindle, KD is required for stabilizing kinetochore MTs, which it probably does by generating tension on the kinetochore, and in its absence, chromosome congression is defective. Finally, depleting KD reduces the velocity of anaphase chromosome motion by ∼40%, without affecting the rate of poleward MT flux. Thus, in addition to its role in silencing the SAC, KD is important for forming and stabilizing K fibers and in powering chromosome motion.Keywords
Funding Information
- National Institutes of Health (40198, 59057)
This publication has 44 references indexed in Scilit:
- Analysis of a RanGTP-regulated gradient in mitotic somatic cellsNature, 2006
- Efficient Mitosis in Human Cells Lacking Poleward Microtubule FluxCurrent Biology, 2005
- Rod–Zw10–Zwilch: a key player in the spindle checkpointTrends in Cell Biology, 2005
- ZW10 links mitotic checkpoint signaling to the structural kinetochoreThe Journal of cell biology, 2005
- Drosophila CLASP is required for the incorporation of microtubule subunits into fluxing kinetochore fibresNature, 2004
- Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle polesThe Journal of cell biology, 2004
- E pluribus unum: towards a universal mechanism for spindle assemblyTrends in Cell Biology, 2004
- Cytoplasmic dynein is localized to kinetochores during mitosisNature, 1990
- Chromosome behavior after laser microirradiation of a single kinetochore in mitotic PtK2 cells.The Journal of cell biology, 1981
- Cell division in two large pennate diatoms Hantzschia and Nitzschia III. A new proposal for kinetochore function during prometaphase.The Journal of cell biology, 1980