Review Article | Published:

A journey into space

Nature Reviews Molecular Cell Biology volume 2, pages 647656 (2001) | Download Citation

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Abstract

The fission yeast, Schizosaccharomyces pombe, has been used as a model eukaryote to study processes such as the cell cycle and cell morphology. In this single-celled organism, growing in a straight line and maintaining the nucleus in the centre of the cell depend on intracellular positional information. Microtubules and microtubular transport are important for generating positional information within the fission yeast cell, and these molecular mechanisms are also probably relevant for generating positional information in other eukaryotic cells.

Key points

  • Microtubules are important components for establishing positional information, and are required to establish a cellular axis and to position the nucleus.

  • Several proteins have been identified that are required to establish an axis. In the absence of these proteins, fission yeast cells no longer grow in a straight line. These proteins include Tea1, Tea2, Tip1, Mal3, γ-tubulin, Alp4 and Alp6, all of which affect microtubule dynamics, and several proteins required for microtubule biogenesis.

  • Many of the proteins identified in fission yeast are also conserved in other organisms. The CLIP170 protein family regulates microtubule dynamics and might be involved in a microtubule guidance mechanism, both in fission yeast and other eukaryotes.

  • Three models have been proposed that might guide microtubules along an axis and identify the ends of the cell. One of these models depends on the presence of historical markers; one depends more on the self organization of microtubules, together with marker proteins that can act as catastrophe factors; and the third depends on the ability of microtubules to withstand pressure. These models are not mutually exclusive.

  • The nucleus might be positioned at the cell centre by a balance of pushing forces generated by interphase microtubules. A second mechanism that positions the daughter nuclei at the cell centre after mitosis might depend on a pulling mechanism so that the nucleus is pulled to the cell centre by the post-anaphase array of microtubules. Microtubules and motor proteins are also required to position the nucleus in other organisms.

  • Similar microtubular behaviour might be the basis of mechanisms to define the long axis of the cell and to position the nucleus at the cell centre.

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References

  1. 1.

    & Molecular machines: putting the pieces together. J. Cell Biol. 152, F1–F10 (2001).

  2. 2.

    One hundred years of positional information. Trends Genet. 12, 359–364 (1996).

  3. 3.

    Die Verebung von homothallie und heterothallie bei Schizosaccharomyces pombe. Compt. Rend. Lab. Carlsberg 24, 381–475 (1950).

  4. 4.

    & Growth in cell length in the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 75, 357–376 (1985).

  5. 5.

    & Localisation of F-actin through the cell-division cycle of Schizosaccharomyces pombe. Eur. J. Cell Biol. 39, 27–32 (1985).

  6. 6.

    & The use of cell division cycle mutants to investigate the control of microtubule distribution in the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 89, 343–357 (1988).

  7. 7.

    , & Three-dimensional reconstruction and analysis of mitotic spindles from the yeast, Schizosaccharomyces pombe. J. Cell Biol. 120, 141–151 (1993).

  8. 8.

    , & New arrays of microtubules in fission yeast Schizosaccharomyces pombe. Protoplasma 188, 252–257 (1995).

  9. 9.

    et al. The fission yeast γ-tubulin is essential for mitosis and is localized at microtubule organizing centers. J. Cell Sci. 99, 693–700 (1991).

  10. 10.

    & Evidence for cell-cycle-specific, spindle pole body-mediated, nuclear positioning in the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 110, 1851–1866 (1997).

  11. 11.

    & Role of γ-tubulin in mitosis-specific microtubule nucleation from the Schizosaccharomyces pombe spindle pole body. J. Cell Sci. 109, 165–177 (1996).

  12. 12.

    , , , & The spindle pole body of Schizosaccharomyces pombe enters and leaves the nuclear envelope as the cell cycle proceeds. Mol. Biol. Cell 8, 1461–1479 (1997).

  13. 13.

    & Mitosis in the fission yeast Schizosaccharomyces pombe as revealed by freeze-substitution electron microscopy. J. Cell Sci. 80, 253–268 (1986).

  14. 14.

    & Mitosis in the fission yeast Schizosaccharomyces pombe: a comparative study with light and electron microscopy. J. Cell Sci. 9, 475–507 (1971).

  15. 15.

    & Microfilaments and cytoplasmic microtubules in cell division cycle mutants of Schizosaccharomyces pombe. Can. J. Microbiol. 26, 250–254 (1980).

  16. 16.

    , & Dynamics of cytoplasmic organelles in the cell cycle of the fission yeast Schizosaccharomyces pombe: three-dimensional reconstruction from serial sections. J. Cell Sci. 94, 647–656 (1989).

  17. 17.

    , , & Identification of the pleiotropic cell division cycle gene nda2 as one of two different α-tubulin genes in Schizosaccharomyces pombe. Cell 37, 233–242 (1984).

  18. 18.

    , , & Two cell division cycle genes NDA2 and NDA3 of the fission yeast Schizosaccharomyces pombe control microtubular organisation and sensitivity to anti-mitotic benzimidazole compounds. J. Mol. Biol. 168, 271–284 (1983).

  19. 19.

    & Dynamic instability of microtubule growth. Nature 312, 237–242 (1984).

  20. 20.

    & Microtubule dynamics in interphase cells. J. Cell Biol. 102, 1020–1031 (1986).

  21. 21.

    et al. Dynamic instability of individual microtubules analyzed by video light microscopy: rate constants and transition frequencies. J. Cell Biol. 107, 1437–1448 (1988).

  22. 22.

    & Beyond self-assembly: from microtubules to morphogenesis. Cell 45, 329–342 (1986).

  23. 23.

    Microtubule dynamics: the view from the tip. Curr. Biol. 10, R860–R862 (2000).

  24. 24.

    & Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 13, 83–117 (1997).

  25. 25.

    , & Structural transitions at microtubule ends correlate with their dynamic properties in Xenopus egg extracts. J. Cell Biol. 149, 767–774 (2000).

  26. 26.

    & Dynamic instability of microtubules as an efficient way to search in space. Proc. Natl Acad. Sci. USA 91, 5682–5685 (1994).

  27. 27.

    , , , & Microtubule nucleation by γ-tubulin-containing rings in the centrosome. Nature 378, 638–640 (1995).

  28. 28.

    , , & Nucleation of microtubule assembly by a γ-tubulin-containing ring complex. Nature 378, 578–583 (1995).

  29. 29.

    , , , & A mechanism for nuclear positioning in fission yeast based on microtubule pushing. J. Cell Biol. 153, 397–411 (2001).Using live imaging and computer simulation these authors have shown that the interphase nucleus can be maintained in the centre of the cell by a balance between pushing forces generating by microtubules.

  30. 30.

    The fission yeast microtubule cytoskeleton. J. Cell Sci. 111, 1603–1612 (1998).

  31. 31.

    & The product of the spindle formation gene sad1+ associates with the fission yeast spindle pole body and is essential for viability. J. Cell Biol. 129, 1033–1047 (1995).

  32. 32.

    & Dynamics of interphase microtubules in Schizosaccharomyces pombe. Curr. Biol. 10, 766–775 (2000).The first detailed description of the behaviour of microtubule bundles in live fission yeast cells; the authors also suggest that microtubules in a bundle are orientated with the plus ends towards the cell tips and the minus ends overlapping close to the equator of the cell.

  33. 33.

    & CLIP170-like tip1p spatially organizes microtubular dynamics in fission yeast. Cell 102, 695–704 (2000).These authors describe how the tea-interacting protein 1 (Tip1) regulates microtubule dynamics. Tip1 is part of a microtubular guidance mechanism that aligns microtubules along the long axis of the cell.

  34. 34.

    , , & Dynamic confocal imaging of interphase and mitotic microtubules in the fission yeast, S. pombe. Biol. Bull. 197, 262–263 (1999).

  35. 35.

    & Genetic analysis of cell morphogenesis in fission yeast — a role for casein kinase II in the establishment of polarized growth. EMBO J. 13, 2066–2074 (1994).

  36. 36.

    , & Fission yeast cell morphogenesis: identification of new genes and analysis of their role during the cell cycle. J. Cell Biol. 131, 1529–1538 (1995).

  37. 37.

    , , , & Identification of novel temperature-sensitive lethal alleles in essential β-tubulin and nonessential α2-tubulin genes as fission yeast polarity mutants. Mol. Biol. Cell 9, 1757–1771 (1998).

  38. 38.

    & Pom1p, a fission yeast protein kinase that provides positional information for both polarized growth and cytokinesis. Genes Dev. 12, 1356–1370 (1998).

  39. 39.

    Fission yeast morphogenesis — posing the problems. Mol. Biol. Cell 5, 613–616 (1994).

  40. 40.

    & Discovering the poles. Trends Cell Biol. 8, 163–167 (1998).

  41. 41.

    , & The NDA3 gene of fission yeast encodes β-tubulin: a cold sensitive nda3 mutation reversibly blocks spindle formation and chromosome movement in mitosis. Cell 39, 349–358 (1984).

  42. 42.

    , , & Cold-sensitive nuclear division arrest mutants of the fission yeast Schizosaccharomyces pombe. J. Mol. Biol. 168, 251–270 (1983).

  43. 43.

    , , & Cell division cycle genes nda2 and nda3 of the fission yeast Schizosaccharomyces pombe control microtubular organization and sensitivity to anti-mitotic benzimidazole compounds. J. Mol. Biol. 168, 271–284 (1983).

  44. 44.

    & Regulation of cell polarity by microtubules in fission yeast. J. Cell Biol. 142, 457–471 (1998).

  45. 45.

    & Tea1 and the microtubular cytoskeleton are important for generating global spatial order within the fission yeast cell. Cell 89, 939–949 (1997).

  46. 46.

    & A kinesin family tree. J. Cell Sci. 113, 3681–3682 (2000).

  47. 47.

    et al. Tea2p is a kinesin-like protein required to generate polarized growth in fission yeast. J. Cell Biol. 151, 15–28 (2000).

  48. 48.

    , , & KinI kinesins are microtubule-destabilizing enzymes. Cell 96, 69–78 (1999).

  49. 49.

    , , & CLIP-170 links endocytic vesicles to microtubules. Cell 70, 887–900 (1992).

  50. 50.

    & CLIPs for organelle–microtubule interactions. Trends Cell Biol. 6, 178–183 (1996).

  51. 51.

    , , & CLIP-170 highlights growing microtubule ends in vivo. Cell 96, 517–527 (1999).

  52. 52.

    et al. CLASPs are CLIP-115 and-170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell 104, 923–935 (2001).These authors have isolated two CLIP 170 (115)-associated proteins and shown that they bind to both CLIPs and microtubules, and affect microtubule stability. CLASPs might be involved in the regional regulation of microtubule dynamics in response to positional cues.

  53. 53.

    , , & Mal3, the fission yeast homologue of the human APC-interacting protein EB-1 is required for microtubule integrity and the maintenance of cell form. J. Cell Biol. 139, 717–728 (1997).

  54. 54.

    , & A conserved interaction between Moe1 and Mal3 is important for proper spindle formation in Schizosaccharomyces pombe. Mol. Biol. Cell 11, 4067–4077 (2000).

  55. 55.

    , , & Regulation and function of the interaction between the APC tumour suppressor protein and EB1. Oncogene 19, 1950–1958 (2000).

  56. 56.

    , & The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules. Curr. Biol. 10, 865–868 (2000).

  57. 57.

    & EB1 proteins regulate microtubule dynamics, cell polarity, and chromosome stability. J. Cell Biol. 149, 761–766 (2000).

  58. 58.

    et al. Microtubules mediate mitochondrial distribution in fission yeast. Proc. Natl Acad. Sci. USA 93, 11664–11668 (1996).

  59. 59.

    , , & Functional dissection and hierarchy of tubulin-folding cofactor homologues in fission yeast. Mol. Biol. Cell 10, 2987–3001 (1999).

  60. 60.

    , & The cofactor-dependent pathways for α- and β-tubulins in microtubule biogenesis are functionally different in fission yeast. Genetics 156, 93–103 (2000).

  61. 61.

    & Sto1p, a fission yeast protein similar to tubulin folding cofactor E, plays an essential role in mitotic microtubule assembly. J. Cell Sci. 112, 1979–1988 (1999).

  62. 62.

    , , & Essential role of tubulin-folding cofactor D in microtubule assembly and its association with microtubules in fission yeast. EMBO J. 17, 658–666 (1998).

  63. 63.

    et al. A mutation in γ-tubulin alters microtubule dynamics and organization and is synthetically lethal with the kinesin-like protein pkl1p. Mol. Biol. Cell 11, 1225–1239 (2000).

  64. 64.

    & The fission yeast γ-tubulin complex is required in G1 phase and is a component of the spindle assembly checkpoint. EMBO J. 19, 6098–6111 (2000).Microtubules in mutants of part of the γ-tubulin complex (altered polarity 4 and 6) are associated with the SPB and are abnormally long, showing that defective polymerization of microtubules can affect their ability to stop growth at the ends of the cells.

  65. 65.

    & New concepts in fission yeast morphogenesis. Phil. Trans R. Soc. Lond. (B) 355, 873–877 (2000).

  66. 66.

    , , & A cytoplasmic dynein heavy chain is required for oscillatory nuclear movement of meiotic prophase and efficient meiotic recombination in fission yeast. J. Cell Biol. 145, 1233–1249 (1999).

  67. 67.

    , , & Oscillatory nuclear movement in fission yeast meiotic prophase is driven by astral microtubules, as revealed by continuous observation of chromosomes and microtubules in living cells. J. Cell Sci. 111, 701–712 (1998).

  68. 68.

    , , & Microtubule-dependent nuclear positioning and nuclear-dependent septum positioning in the fission yeast Saccharomyces pombe. Biol. Bull. 199, 205–206 (2000).

  69. 69.

    , & Intramitotic controls in the fission yeast Schizosaccharomyces pombe: the effect of cell size on spindle length and the timing of mitotic events. J. Cell Biol. 110, 1617–1621 (1990).

  70. 70.

    , , , & Live analysis of lagging chromosomes during anaphase and their effect on spindle elongation rate in fission yeast. J. Cell Sci. 113, 4177–4191 (2000).

  71. 71.

    & Mechanisms of nuclear positioning. J. Cell Sci. 111, 2283–2295 (1998).

  72. 72.

    et al. Preparation of modified tubulins. Methods Enzymol. 128, 478–485 (1991).

  73. 73.

    & The role of nucleation in patterning microtubule networks. J. Cell Sci. 111, 2077–2083 (1998).

  74. 74.

    , , & Physical properties determining self-organization of motors and microtubules. Science 292, 1167–1171 (2001).

  75. 75.

    et al. Cell wall formation in regenerating protoplasts of Schizosaccharomyces pombe: study by high resolution, low voltage scanning electron microscopy. J. Electron Microsc. (Tokyo) 38, 457–468 (1989).

  76. 76.

    & Focal adhesions: structure and dynamics. Biol. Cell 92, 477–494 (2000).

  77. 77.

    Extracellular matrix interactions with the apical surface of vascular endothelial cells. J. Cell Sci. 76, 1–16 (1985).

  78. 78.

    & Integrin affinity modulation. Trends Cell Biol. 8, 359–364 (1998).

  79. 79.

    , & New perspectives on mechanisms involved in generating epithelial cell polarity. Physiol. Rev. 79, 73–98 (1999).

  80. 80.

    , , & Reorganization of the cytoskeleton during Drosophila oogenesis: implications for axis specification and intercellular transport. Development 115, 923–936 (1992).

  81. 81.

    , , , & Drosophila par-1 is required for oocyte differentiation and microtubule organization. Curr. Biol. 11, 75–87 (2001).

  82. 82.

    & Polarization of the anterior–posterior axis of C. elegans is a microtubule-directed process. Nature 408, 89–92 (2000).

  83. 83.

    , & The spd-2 gene is required for polarization of the anteroposterior axis and formation of the sperm asters in the Caenorhabditis elegans zygote. Dev. Biol. 222, 55–70 (2000).The experiments, elimination or ectopic positioning of sperm asters, described in references 82 and 83, have shown that these microtubules are likely to direct polarity of the embryonic axis.

  84. 84.

    & Dynamic microtubules and specification of the zebrafish embryonic axis. Curr. Biol. 7, 31–42 (1997).

  85. 85.

    , , , & Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nature Cell Biol. 1, 45–50 (1999).

  86. 86.

    & Relationship between microtubule dynamics and lamellipodium formation revealed by direct imaging of microtubules in cells treated with nocodazole or taxol. Cell. Motil. Cytoskeleton 41, 325–340 (1998).

  87. 87.

    , & The role of microtubule dynamics in growth cone motility and axonal growth. J. Cell Biol. 128, 139–155 (1995).

  88. 88.

    Polarization of pseudopodial activities: cytoskeletal mechanisms. J. Cell Sci. 98, 1–4 (1991).

  89. 89.

    , & Pseudopodial activity at the active edge of migrating fibroblast is decreased after drug-induced microtubule depolymerization. Cell. Motil. Cytoskeleton 19, 152–158 (1991).

  90. 90.

    , , , & Protein kinase C activation promotes microtubule advance in neuronal growth cones by increasing average microtubule growth lifetimes. J. Cell Biol. 152, 1033–1044 (2001).

  91. 91.

    & Role of microtubules in random cell migration: stabilization of cell polarity. Cell. Motil. Cytoskeleton 27, 88–96 (1994).

  92. 92.

    , , & Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes. J. Cell Biol. 150, 989–1000 (2000).

  93. 93.

    , , & Actin-dependent lamellipodia formation and microtubule-dependent tail retraction control-directed cell migration. Mol. Biol. Cell 11, 2999–3012 (2000).

  94. 94.

    Regional regulation of microtubule dynamics in polarized, motile cells. Cell. Motil. Cytoskeleton 42, 48–59 (1999).Describes experiments showing that the dynamics of microtubules are regionally regulated. By examining individual microtubules, the author shows that microtubules at the leading edge of polarized motile cells show more persistent growth than those at the lateral edges.

  95. 95.

    & Region-specific microtubule transport in motile cells. J. Cell Biol. 151, 1003–1012 (2000).

  96. 96.

    , & Targeting, capture, and stabilization of microtubules at early focal adhesions. J. Cell Biol. 142, 181–190 (1998).

  97. 97.

    , & Microtubule targeting of substrate contact promotes their relaxation and dissociation. J. Cell Biol. 146, 1033–1043 (1999).

  98. 98.

    , , & Accumulation of a microtubule-binding protein, pp170, at desmosomal plaques. J. Cell Biol. 117, 813–824 (1992).

  99. 99.

    , , , & Nonuniform microtubular polarity established by CHO1/MKLP1 motor protein is necessary for process formation of podocytes. J. Cell Biol. 143, 1961–1970 (1998).

  100. 100.

    et al. Microtubule-dependent control of cell shape and pseudopodial activity is inhibited by the antibody to kinesin motor domain. J. Cell Biol. 123, 1811–1820 (1993).

  101. 101.

    et al. Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829–837 (1998).

  102. 102.

    , , & Assembly and positioning of microtubule asters in microfabricated chambers. Proc. Natl Acad. Sci. USA 94, 6228–6231 (1997).

  103. 103.

    & Self-centring activity of cytoplasm. Nature 386, 170–173 (1997).

  104. 104.

    , & Cytoplasmic dynein is involved in nuclear migration in Aspergillus nidulans. Proc. Natl Acad. Sci. USA 91, 2100–2104 (1994).

  105. 105.

    , , & Genetic interactions among cytoplasmic dynein, dynactin, and nuclear distribution mutants of Neurospora crassa. Proc. Natl Acad. Sci. USA 93, 4775–4780 (1996).

  106. 106.

    et al. The Aspergillus cytoplasmic dynein heavy chain and NUDF localize to microtubule ends and affect microtubule dynamics. Curr. Biol. 11, 719–724 (2001).

  107. 107.

    & Movement of nuclei along microtubules in Xenopus egg extracts. Curr. Biol. 7, 211–214 (1997).

  108. 108.

    , , , & Cytoplasmic dynein is required for the nuclear attachment and migration of centrosomes during mitosis in Drosophila. J. Cell Biol. 146, 597–608 (1999).

  109. 109.

    et al. Dynein motor regulation stabilizes interphase microtubule arrays and determines centrosome position. EMBO J. 18, 6786–6792 (1999).

  110. 110.

    & Investigations into the control of cell form and polarity: the use of morphological mutants in fission yeast. Development S289–S299 (1993).

  111. 111.

    & A Schizosaccharomyces pombe gene encoding a novel polypeptide with a predicted α-helical rod structure found in myosin and intermediate filament families of proteins. Biochim. Biophys. Acta 1399, 67–72 (1998).

  112. 112.

    Genetic analysis of resistant mutants to antimitotic benzimidazole compounds in Schizosaccharomyces pombe. Mol. Gen. Genet. 180, 231–234 (1980).

  113. 113.

    , , & Differential expressions of essential and nonessential α-tubulin genes in Schizosaccharomyces pombe. Mol. Cell. Biol. 6, 2168–2178 (1986).

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Acknowledgements

We would like to thank everyone in the cell-cycle lab at ICRF, particularly Heidi Browning and Teresa Niccoli for their useful comments. We are also very grateful to Bela Novak, Bela Gyoffy, Attila Csikasz-Nagy and Akos Sveiczer at the Budapest University of Technology and Economics for fruitful discussions at the workshop on morphology held in Budapest, May 2000.

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Affiliations

  1. Cell Cycle Laboratory, Imperial Cancer Research Fund, PO Box 123, Lincoln's Inn Fields, London, WC2A 3PX, UK.

    • Jacqueline Hayles
    •  & Paul Nurse
  2. hayles@icrf.icnet.uk

    • Jacqueline Hayles

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Glossary

MICROTUBULE-ORGANIZING CENTRE

A γ-tubulin-containing region from which microtubules are polymerized.

CATASTROPHE

Rapid shrinkage of microtubules from their plus ends, due to loss of α/β-subunits.

KELCH REPEATS

A domain covering repeats of 50 amino acids containing conserved residues, which folds into a β-propeller secondary structure, first identified in kelch proteins and found in several actin-binding proteins.

COILED-COIL

A region of protein secondary structure that might be involved in protein–protein interactions.

KINESIN MOTOR DOMAIN

A conserved region of 350 amino acids, defining members of the kinesin superfamily and required for ATP-dependent translocation along microtubules.

CLIP170 PROTEIN FAMILY

Proteins found at the tips of microtubules and involved in microtubule stability; initially described as linking microtubules to vesicles.

CENTROSOMES

The microtubule-organizing centres in higher eukaryotes; associated with the mitotic spindle and astral microtubules and from which microtubules radiate during interphase.

DESMOSOMAL PLAQUES

Regions of anchorage linking adjacent cells and containing intracellular attachment proteins and transmembrane linker glycoproteins.

PRONUCLEUS

The nucleus from an egg or sperm that contains a single copy of each chromosome pair.

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https://doi.org/10.1038/35089520

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