Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Targeted movement of cell end factors in fission yeast

Abstract

Kinesins are microtubule-based motor proteins that transport cargo to specific locations within the cell. However, the mechanisms by which cargoes are directed to specific cellular locations have remained elusive. Here, we investigated the in vivo movement of the Schizosaccharomyces pombe kinesin Tea2 to establish how it is targeted to microtubule tips and cell ends. Tea2 is loaded onto microtubules in the middle of the cell, in close proximity to the nucleus, and then travels using its intrinsic motor activity primarily at the tips of polymerizing microtubules. The microtubule-associated protein Mal3, an EB1 homologue, is required for loading and/or processivity of Tea2 and this function can be substituted by human EB1. In addition, the cell-end marker Tea1 is required to anchor Tea2 to cell ends. Movement of Tea1 and the CLIP170 homologue Tip1 to cell ends is abolished in Tea2 rigor (ATPase) mutants. We propose that microtubule-based transport from the vicinity of the nucleus to cell ends can be precisely regulated, with Mal3 required for loading/processivity, Tea2 for movement and Tea1 for cell-end anchoring.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: In vivo analysis of Tea2 movement.
Figure 2: Localization of Tea2 rigor proteins.
Figure 3: Phenotypic characterization of tea2 rigor mutants.
Figure 4: Interactions of Tea2 and Mal3.
Figure 5: Transfer and anchoring of Tea2–GFP to cell ends.

Similar content being viewed by others

References

  1. Hayles, J. & Nurse, P. A journey into space. Nature Rev. Mol. Cell. Biol. 2, 647–656 (2001).

    Article  CAS  Google Scholar 

  2. Drummond, D.R. & Cross, R.A. Dynamics of interphase microtubules in Schizosaccharomyces pombe. Curr. Biol. 10, 766–775 (2000).

    Article  CAS  Google Scholar 

  3. Tran, P.T., Marsh, L., Doye, V., Inoué, S. & Chang, F. A mechanism for nuclear positioning in fission yeast based on microtubule pushing. J. Cell Biol. 153, 397–411 (2001).

    Article  CAS  Google Scholar 

  4. Browning, H., Hayles, J., Mata, J., Aveline, L., Nurse, P. & McIntosh, J.R. Tea2p is a kinesin-like protein required to generate polarized growth in fission yeast. J. Cell Biol. 151, 15–27 (2000).

    Article  CAS  Google Scholar 

  5. Meluh, P. & Rose, M. KAR3, a kinesin-related gene required for yeast nuclear fusion. Cell 60, 1029–1041 (1990).

    Article  CAS  Google Scholar 

  6. Nakata, T. & Hirokawa, N. Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport. J. Cell Biol. 131, 1039–1053 (1995).

    Article  CAS  Google Scholar 

  7. Rice, S. et al. A structural change in the kinesin motor protein that drives motility. Nature 402, 778–784 (1999).

    Article  CAS  Google Scholar 

  8. Yun, M., Zhang, X., Park, C.G., Park, H.W. & Endow, S.A. A structural pathway for activation of the kinesin motor ATPase. EMBO J. 20, 2611–2618 (2001).

    Article  CAS  Google Scholar 

  9. Brunner, D. & Nurse, P. CLIP170-like tip1p spatially organises microtubular dynamics in fission yeast. Cell 102, 695–704 (2000).

    Article  CAS  Google Scholar 

  10. Mata, J. & Nurse, P. Tea1 and the microtubule cytoskeleton are important for generating global spatial order within the fission yeast cell. Cell 89, 939–949 (1997).

    Article  CAS  Google Scholar 

  11. Behrens, R. & Nurse, P. Roles of fission yeast tea1p in the localization of polarity factors and in organizing the microtubular cytoskeleton. J. Cell Biol. 157, 783–793 (2002).

    Article  CAS  Google Scholar 

  12. Niccoli, T. & Nurse, P. Different mechanisms of cell polarisation in vegetative and shmooing growth in fission yeast. J. Cell Sci. 115, 1651–1662 (2002).

    CAS  PubMed  Google Scholar 

  13. Beinhauer, J., Hagan, I., Hegemann, J. & Fleig, U. 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).

    Article  CAS  Google Scholar 

  14. Tirnauer, J.S. & Bierer, B.E. EB1 proteins regulate microtubule dynamics, cell polarity, and chromosome stability. J. Cell Biol. 149, 761–766 (2000).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Glynn, J.M., Lustig, R.J., Berlin, A. & Chang, F. Role of bud6p and tea1p in the interaction between actin and microtubules for the establishment of cell polarity in fission yeast. Curr. Biol. 11, 836–845 (2001).

    Article  CAS  Google Scholar 

  17. Jin, H. & Amberg, D.C. Fission yeast Aip3p (spAip3p) is required for an alternative actin-directed polarity program. Mol. Biol. Cell 12, 1275–1291 (2001).

    Article  CAS  Google Scholar 

  18. Schuyler, S.C. & Pellman, D. Microtubule “Plus-end-tracking proteins”: the end is just the beginning. Cell 105, 421–424 (2001).

    Article  CAS  Google Scholar 

  19. Maekawa, H., Usui, T., Knop, M. & Schiebel, E. Yeast Cdk1 translocates to the plus end of cytoplasmic microtubules to regulate bud cortex interactions. EMBO J. 22, 438–449 (2003).

    Article  CAS  Google Scholar 

  20. Bienz, M. Spindles cotton on to junctions, APC and EB1. Nature Cell Biol. 3, E1–E3 (2001).

    Article  Google Scholar 

  21. Askham, J.M., Moncur, P., Markham, A.F. & Morrison, E.E. Regulation and function of the interaction between the APC tumour suppressor protein and EB1. Oncogene 19, 1950–1958 (2000).

    Article  CAS  Google Scholar 

  22. Bloom, K. It's a kar9ochore to capture microtubules. Nature Cell Biol. 2, E96–E98 (2000).

    Article  CAS  Google Scholar 

  23. Mimori-Kiyosue, Y., Shiina, N. & Tsukita, S. Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells. J. Cell Biol. 148, 505–517 (2000).

    Article  CAS  Google Scholar 

  24. Allan, V. & Näthke, I.S. Catch and pull a microtubule: getting a grasp on the cortex. Nature Cell Biol. 3, E226–E228 (2001).

    Article  CAS  Google Scholar 

  25. Jimbo, T. et al. Identification of a link between the tumour suppressor APC and the kinesin superfamily. Nature Cell Biol. 4, 323–327 (2002).

    Article  CAS  Google Scholar 

  26. Kusch, J., Meyer, A., Snyder, M.P. & Barral, Y. Microtubule capture by the cleavage apparatus is required for proper spindle positioning in yeast. Genes Dev. 16, 1627–1639 (2002).

    Article  CAS  Google Scholar 

  27. Chen, C.-R., Chen, J. & Chang, E.C.A. A conserved interaction between Moe1 and Mal3 is important for proper spindle formation in Schizosaccharomyces pombe. Mol. Biol. Cell 11, 4067–4077 (2000).

    Article  CAS  Google Scholar 

  28. Nakamura, M., Zhou, X.Z. & Lu, K.P. Critical role for the EB1 and APC interaction in the regulation of microtubule polymerization. Curr. Biol. 11, 1062–1067 (2001).

    Article  CAS  Google Scholar 

  29. Moreno, S., Klar, A. & Nurse, P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 194, 795–823 (1991).

    Article  CAS  Google Scholar 

  30. West, R.R., Malmstrom, T., Troxell, C.L. & McIntosh, J.R. Two related kinesins, klp5+ and klp6+, foster microtubule disassembly and are required for meiosis in fission yeast. Mol. Biol. Cell 12, 3919–3932 (2001).

    Article  CAS  Google Scholar 

  31. Bahler, J. et al. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast 14, 943–951 (1998).

    Article  CAS  Google Scholar 

  32. Woods, A. et al. Definition of individual components within the cytoskeleton of Trypanosoma brucei by a library of monoclonal antibodies. J. Cell Sci. 93, 491–500 (1989).

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank T. Toda, T. Niccoli, K. Leonhard and S. Castagnetti for critical reading of the manuscript, members of Cancer Research UK light microscopy facility for help with image acquisition and analysis, members of the Cell Cycle lab for helpful discussions and suggestions, J. R. McIntosh and R. West (University of Colorado, Boulder) for fruitful discussions and critical reading of the manuscript, A. Decottignies and P. Zarzov for advice on construction of mutant alleles, U. Fleig for pREPEB1 (Heinrich-Heine-Universitat Dusseldorf) and N. Peat for help with the manuscript. This work was supported by Cancer Research UK (formerly the Imperial Cancer Research Fund), a postdoctoral fellowship to H. Browning from the International Agency for Research on Cancer, and grant NS28562 to D. Hackney.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heidi Browning.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Browning, H., Hackney, D. & Nurse, P. Targeted movement of cell end factors in fission yeast. Nat Cell Biol 5, 812–818 (2003). https://doi.org/10.1038/ncb1034

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1034

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing