Home LiteratureArticle Details
PMID: 8898361 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The kinetochore microtubule minus-end disassembly associated with poleward flux produces a force that can do work.

Molecular biology of the cell ·Vol. 7 ·No. 10 ·1996-10-00 ·Pages 1547-58

Waters JC, Mitchison TJ, Rieder CL, Salmon ED

Abstract

During metaphase and anaphase in newt lung cells, tubulin subunits within the kinetochore microtubule (kMT) lattice flux slowly poleward as kMTs depolymerize at their minus-ends within in the pole. Very little is known about how and where the force that moves the tubulin subunits poleward is generated and what function it serves during mitosis. We found that treatment with the drug taxol (10 microM) caused separated centrosomes in metaphase newt lung cells to move toward one another with an average velocity of 0.89 microns/min, until the interpolar distance was reduced by 22-62%. This taxol-induced spindle shortening occurred as kMTs between the chromosomes and the poles shortened. Photoactivation of fluorescent marks on kMTs revealed that taxol inhibited kinetochore microtubule assembly/disassembly at kinetochores, whereas minus-end MT disassembly continued at a rate typical of poleward flux in untreated metaphase cells. This poleward flux was strong enough to stretch the centromeric chromatin between sister kinetochores as much as it is stretched in control metaphase cells. In anaphase, taxol blocked kMT disassembly/assembly at the kinetochore whereas minus-end disassembly continued at a rate similar to flux in control cells (approximately 0.2 microns/min). These results reveal that the mechanism for kMT poleward flux 1) is not dependent on kMT plus-end dynamics and 2) produces pulling forces capable of generating tension across the centromeres of bioriented chromosomes.

MeSH Terms
Anaphase Animals Biomechanical Phenomena Cell Polarity Cells, Cultured Chromatin/ultrastructure Image Processing, Computer-Assisted Kinetochores/drug effects,physiology Lung/cytology Metaphase Microscopy, Fluorescence Microtubules/drug effects,physiology Paclitaxel/pharmacology Photochemistry Salamandridae Spindle Apparatus/drug effects,physiology Stress, Mechanical Tubulin/metabolism
Chemicals
Chromatin Tubulin Paclitaxel
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Waters J C
Department of Biology, University of North Carolina, Chapel Hill 27599-3280, USA.
Mitchison T J
Rieder C L
Salmon E D
References (48)
48 references, click to expand
  1. Taxol stabilizes microtubules in mouse fibroblast cells.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1561-5 PMID: 6103535
  2. Chromosomes move poleward in anaphase along stationary microtubules that coordinately disassemble from their kinetochore ends.
    J Cell Biol. 1987 Jan;104(1):9-18 PMID: 3793763
  3. Force generation by microtubule assembly/disassembly in mitosis and related movements.
    Mol Biol Cell. 1995 Dec;6(12):1619-40 PMID: 8590794
  4. Kinetochore microtubule dynamics and the metaphase-anaphase transition.
    J Cell Biol. 1995 Nov;131(3):721-34 PMID: 7593192
  5. The spindle-assembly checkpoint: aiming for a perfect mitosis, every time.
    Trends Cell Biol. 1996 Jun;6(6):228-34 PMID: 15157461
  6. The force-producing mechanism for centrosome separation during spindle formation in vertebrates is intrinsic to each aster.
    J Cell Biol. 1993 Jul;122(2):361-72 PMID: 8320259
  7. NuMA is required for the organization of microtubules into aster-like mitotic arrays.
    J Cell Biol. 1995 Nov;131(3):693-708 PMID: 7593190
  8. High resolution multimode digital imaging system for mitosis studies in vivo and in vitro.
    Biol Bull. 1994 Oct;187(2):231-2 PMID: 7811791
  9. LOCAL REDUCTION OF SPINDLE FIBER BIREFRINGENCE IN LIVING NEPHROTOMA SUTURALIS (LOEW) SPERMATOCYTES INDUCED BY ULTRAVIOLET MICROBEAM IRRADIATION.
    J Cell Biol. 1965 Apr;25:SUPPL:95-117 PMID: 14342833
  10. Chromosome behavior after laser microirradiation of a single kinetochore in mitotic PtK2 cells.
    J Cell Biol. 1981 Mar;88(3):543-53 PMID: 7194343
  11. Evidence that kinetochore microtubules in crane-fly spermatocytes disassemble during anaphase primarily at the poleward end.
    J Cell Sci. 1994 Nov;107 ( Pt 11):3015-27 PMID: 7699001
  12. Motile kinetochores and polar ejection forces dictate chromosome position on the vertebrate mitotic spindle.
    J Cell Biol. 1994 Feb;124(3):223-33 PMID: 8294508
  13. A new role for motor proteins as couplers to depolymerizing microtubules.
    J Cell Biol. 1995 Jan;128(1-2):1-4 PMID: 7822407
  14. Poleward force at the kinetochore in metaphase depends on the number of kinetochore microtubules.
    J Cell Biol. 1990 Feb;110(2):391-404 PMID: 2298810
  15. Characterization of the mitotic traction system, and evidence that birefringent spindle fibers neither produce nor transmit force for chromosome movement.
    Chromosoma. 1966;19(1):44-98 PMID: 5330243
  16. Substoichiometric binding of taxol suppresses microtubule dynamics.
    Biochemistry. 1995 Feb 21;34(7):2203-11 PMID: 7857932
  17. Oscillatory movements of monooriented chromosomes and their position relative to the spindle pole result from the ejection properties of the aster and half-spindle.
    J Cell Biol. 1986 Aug;103(2):581-91 PMID: 3733881
  18. Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex.
    Nature. 1995 Dec 7;378(6557):578-83 PMID: 8524390
  19. Riding the polar winds: chromosomes motor down east.
    Cell. 1995 Apr 7;81(1):5-8 PMID: 7720073
  20. Pole-to-chromosome movements induced at metaphase: sites of microtubule disassembly.
    J Cell Sci. 1991 Sep;100 ( Pt 1):205-11 PMID: 1795025
  21. Studies on the ejection properties of asters: astral microtubule turnover influences the oscillatory behavior and positioning of mono-oriented chromosomes.
    J Cell Sci. 1991 Aug;99 ( Pt 4):701-10 PMID: 1685159
  22. Newt lung epithelial cells: cultivation, use, and advantages for biomedical research.
    Int Rev Cytol. 1990;122:153-220 PMID: 2246116
  23. Kinetochores are transported poleward along a single astral microtubule during chromosome attachment to the spindle in newt lung cells.
    J Cell Biol. 1990 Jan;110(1):81-95 PMID: 2295685
  24. Poleward microtubule flux mitotic spindles assembled in vitro.
    J Cell Biol. 1991 Mar;112(5):941-54 PMID: 1999464
  25. Mutants of the Drosophila ncd microtubule motor protein cause centrosomal and spindle pole defects in mitosis.
    J Cell Sci. 1994 Apr;107 ( Pt 4):859-67 PMID: 8056842
  26. Polewards microtubule flux in the mitotic spindle: evidence from photoactivation of fluorescence.
    J Cell Biol. 1989 Aug;109(2):637-52 PMID: 2760109
  27. Kinetochores, microtubules and the metaphase checkpoint.
    Trends Cell Biol. 1995 Apr;5(4):143-8 PMID: 14732139
  28. Tension, microtubule rearrangements, and the proper distribution of chromosomes in mitosis.
    Chromosoma. 1989 Jun;98(1):33-9 PMID: 2766878
  29. Tubulin flux in the mitotic spindle: where does it come from, where is it going?
    Cell Motil Cytoskeleton. 1990;16(2):93-8 PMID: 2198113
  30. Microtubule flux in mitosis is independent of chromosomes, centrosomes, and antiparallel microtubules.
    Mol Biol Cell. 1994 Feb;5(2):217-26 PMID: 8019007
  31. Identification of a minus end-specific microtubule-associated protein located at the mitotic poles in cultured mammalian cells.
    Eur J Cell Biol. 1991 Apr;54(2):255-67 PMID: 1679010
  32. Monoclonal antibodies specific for thiophosphorylated proteins recognize Xenopus MPF.
    Dev Biol. 1988 Sep;129(1):209-16 PMID: 3044877
  33. Microtubule assembly and kinetochore directional instability in vertebrate monopolar spindles: implications for the mechanism of chromosome congression.
    J Cell Sci. 1994 Jan;107 ( Pt 1):285-97 PMID: 8175915
  34. Differential expression of a phosphoepitope at the kinetochores of moving chromosomes.
    J Cell Biol. 1993 Sep;122(6):1311-21 PMID: 7690762
  35. Microtubule dynamics during the cell cycle: the effects of taxol and nocodazole on the microtubule system of Pt K2 cells at different stages of the mitotic cycle.
    Int Rev Cytol. 1986;101:215-74 PMID: 2870994
  36. Kinetochore microtubules shorten by loss of subunits at the kinetochores of prometaphase chromosomes.
    J Cell Sci. 1991 Feb;98 ( Pt 2):151-8 PMID: 2055954
  37. Microtubule treadmills--possible molecular machinery.
    Nature. 1981 Oct 29;293(5835):705-11 PMID: 7027052
  38. Yeast Kar3 is a minus-end microtubule motor protein that destabilizes microtubules preferentially at the minus ends.
    EMBO J. 1994 Jun 1;13(11):2708-13 PMID: 7912193
  39. Chromosome micromanipulation. 3. Spindle fiber tension and the reorientation of mal-oriented chromosomes.
    J Cell Biol. 1969 Oct;43(1):40-50 PMID: 5824068
  40. Structural and mechanical control of mitotic progression.
    Cold Spring Harb Symp Quant Biol. 1991;56:613-9 PMID: 1819511
  41. Motors involved in spindle assembly and chromosome segregation.
    Curr Opin Cell Biol. 1996 Feb;8(1):4-9 PMID: 8791405
  42. Microtubule nucleation by gamma-tubulin-containing rings in the centrosome.
    Nature. 1995 Dec 7;378(6557):638-40 PMID: 8524401
  43. Kinetochore motility after severing between sister centromeres using laser microsurgery: evidence that kinetochore directional instability and position is regulated by tension.
    J Cell Sci. 1995 Jul;108 ( Pt 7):2537-48 PMID: 7593295
  44. Identification of katanin, an ATPase that severs and disassembles stable microtubules.
    Cell. 1993 Nov 5;75(3):419-29 PMID: 8221885
  45. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle.
    J Cell Biol. 1994 Dec;127(5):1301-10 PMID: 7962091
  46. Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism.
    J Cell Biol. 1993 Aug;122(4):859-75 PMID: 8349735
  47. Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.
    Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9552-6 PMID: 8105478
  48. Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A in newt lung cell mitosis.
    J Cell Biol. 1992 Nov;119(3):569-82 PMID: 1400593
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
Published
1996-10-00
Pages
1547-58
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC276005
Subset
IM
Grants
NIGMS NIH HHS · GM-24364 · United States
NIGMS NIH HHS · GM-29565 · United States
NIGMS NIH HHS · GM-40198 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]