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The Contribution of the C-Terminal Tails of Microtubules in Altering the Force Production Specifications of Multiple Kinesin-1

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Abstract

The extent to which beta tubulin isotypes contribute to the function of microtubules and the microtubule-driven transport of molecular motors is poorly understood. The major differences in these isotypes are associated with the structure of their C-terminal tails. Recent studies have revealed a few aspects of the C-terminal tails’ regulatory role on the activities of some of the motor proteins on a single-molecule level. However, little attention is given to the degree to which the function of a team of motor proteins can be altered by the microtubule’s tail. In a set of parallel experiments, we investigated this open question by studying the force production of several kinesin-1 (kinesin) molecular motors along two groups of microtubules: regular ones and those microtubules whose C-terminals are cleaved by subtilisin digestion. The results indicate that the difference between the average of the force production of motors along two types of microtubules is statistically significant. The underlying mechanism of such production is substantially different as well. As compared to untreated microtubules, the magnitude of the binding time of several kinesin-1 is almost three times greater along subtilisin-treated microtubules. Also, the velocity of the group of kinesin molecules shows a higher sensitivity to external loads and reduces significantly under higher loads along subtilisin-treated microtubules. Together, this work shows the capacity of the tails in fine-tuning the force production characteristics of several kinesin molecules.

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References

  1. Howard, J. (2001). Mechanics of motor proteins and the cytoskeleton. Sunderland, MA: Sinauer Associates.

    Google Scholar 

  2. Hirokawa, N., Noda, Y., & Tanaka, Y., et al. (2009). Kinesin superfamily motor proteins and intracellular transport. Nature Reviews Molecular Cell Biology, 10, 682–696.

    Article  CAS  PubMed  Google Scholar 

  3. Skoufias, D. A., & Scholey, J. M. (1993). Cytoplasmic microtubule-base motor proteins. Current Opinion in Cell Biology, 5, 95–107.

    Article  CAS  PubMed  Google Scholar 

  4. Vale, R. D. (2003). The molecular motor toolbox for intracellular transport. Cell, 112, 467–480.

    Article  CAS  PubMed  Google Scholar 

  5. Mallik, R., & Gross, S. P. (2004). Molecular motors: strategies to get along. Current Biology, 14, 971–982.

    Article  Google Scholar 

  6. Raff, E. C., Fackenthal, J. D., Hutchens, J. A., et al. (1997). Microtubule architecture specified by a β-tubulin isoform. Science, 275, 70–73.

    Article  CAS  PubMed  Google Scholar 

  7. Luuduena, R. F. (1993). Are tubulin isotypes functionally significant? Molecular Biology of the Cell, 4, 445–457.

    Article  Google Scholar 

  8. Krauhs, E., Little, M., Kempf, T., Hofer-Warbinek, R., et al. (1981). Complete amino acid sequence of beta-tubulin from porcine brain. Proceedings of the National Academy of Sciences, 78, 4156–4160.

    Article  CAS  Google Scholar 

  9. Newton, C. N., DeLuca, J. G., Himes, R. H., et al. (2002). Intrinsically slow dynamic instability of HeLa cell microtubules in vitro. Journal of Biological Chemistry, 277, 42456–42462.

    Article  CAS  PubMed  Google Scholar 

  10. Feizabadi, M. S., Mutafopulos, K., & Behr, A. (2011). Measuring the persistence length of MCF7 cell microtubules in vitro. Biotechnology Journal, 6, 882–887.

    Article  CAS  PubMed  Google Scholar 

  11. Feizabadi, M. S., & Jun, Y. (2014). Kinesin-1 translocation: surprising differences between bovine brain and MCF7-drived microtubules. Biochemical and Biophysical Research Communications, 4, 543–546.

    Article  Google Scholar 

  12. Sirajuddin, M., Rice, L. M., & Vale, R. D. (2014). Regulation of microtubule motors by tubulin isotypes and post-translational modifications. Nature Cell Biology, 16, 335–344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Verhey, K. J., & Gaerting, J. (2007). The tubulin code. Cell Cycle, 6, 2152–2160.

    Article  CAS  PubMed  Google Scholar 

  14. Feizabadi, M. S., Janakaloti Narayanareddy, B. R., Vadpey, O., et al. (2015). Microtubule c-terminal tails can change characteristics of motor force production. Traffic, 16, 1075–1087.

    Article  Google Scholar 

  15. Wang, Z., & Sheetz, M. P. (2000). The C-terminus of tubulin increases cytoplasmic dynein and kinesin processivity. Biophysical Journal, 78, 1955–1964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Welte, M. A., Gross, S. P., Postner, M., et al. (1998). Developmental regulation of vesicle transport in drosophilia embryos: force and kinetics. Cell, 92, 547–557.

    Article  CAS  PubMed  Google Scholar 

  17. Vershinin, M., Carter, B. C., Razafsky, D. S., et al. (2007). Multiple-motor based transport and its regulation by Tau. Proceedings of the National Academy of Sciences, 104, 87–92.

    Article  CAS  Google Scholar 

  18. Hendricks, A. G., Holzbaur, E. L., & Goldman, Y. E. (2012). Force measurements on cargoes in living cells reveal collective dynamics of microtubule motors. Proceedings of the National Academy of Sciences, 109, 18447–18452.

    Article  CAS  Google Scholar 

  19. Beeg, J., Klumpp, S., Dimova, R., et al. (2008). Transport of beads by several kinesin motors. Biophysical Journal, 94, 532–541.

    Article  CAS  PubMed  Google Scholar 

  20. Furutaa, K., Furutaa, A., Toyoshimab, Y. Y., et al. (2013). Measuring collective transport by defined numbers of processive and nonprocessive kinesin motors. Proceedings of the National Academy of Sciences, 110, 501–506.

    Article  Google Scholar 

  21. Shalli, K., Brown, I., Heys, S. D., et al. (2005). Alterations of b-tubulin isotypes in breast cancer cells resistant to docetaxel. FASEB Journal, 19, 1299–1301.

    CAS  PubMed  Google Scholar 

  22. Hiser, L., Aggarwal, A., Young, R., et al. (2006). Comparison of b-tubulin mRNA and protein levels in 12 human cancer cell lines. Cell Motility and the Cytoskeleton, 63, 41–52.

    Article  CAS  PubMed  Google Scholar 

  23. Xu, J., Reddy, B. J., Anand, P., et al. (2012). Casein kinase 2 reverses tail-independent inactivation of kinesin-1. Nature Communications, 3, 754.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Smith, T. A., Hong, W., Zachariah, M. M., et al. (2013). Single-molecule inhibition of human kinesin by adociasulfate-13 and -14 from the sponge Cladocroce aculeate. Proceedings of the National Academy of Sciences, 110(47), 18880–18885.

    Article  CAS  Google Scholar 

  25. Jun, Y., Tripathy, S. K., Narayanareddy, B. R. J., et al. (2014). Calibration of optical tweezers for in vivo force measurements: how do different approaches compare? Biophysical Journal, 107, 1474–1484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Thorn, K. S., Ubersax, J. A., & Vale, R. D. (2000). Engineering the processive run length of the kinesin motor. Journal of Cell Biology, 151, 1093–1100.

    Article  Google Scholar 

  27. Luchko, T., Huzil, J. T., Stepanova, M., et al. (2008). Conformational analysis of the carboxy-terminal tails of human beta-tubulin isotypes. Biophysical Journal, 94, 1971–1982.

    Article  CAS  PubMed  Google Scholar 

  28. Prodromou, C., Panaretou, B., Chohan, S., et al. (2000). The ATPase cycle of Hsp90 drives a molecular ‘clamp’ via transient dimerization of N-terminal domains. EMBO Journal, 19, 4383–4393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Atherton, J., Farabella, I., Yu, I., et al. (2014). Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins. eLife, 3, e03680.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Kunwar, A., Vershinin, M., Gross, S. P. (2008). Stepping, strain gating, and an unexpected force-velocity curve for multiple-motor-based transport. Current Biology, 18, 1173–1183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgment

The author thanks members of the Gross laboratory (University of California at Irvine) for providing kinesin protein, technical help, and useful discussions.

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Correspondence to Mitra Shojania Feizabadi.

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Feizabadi, M.S. The Contribution of the C-Terminal Tails of Microtubules in Altering the Force Production Specifications of Multiple Kinesin-1. Cell Biochem Biophys 74, 373–380 (2016). https://doi.org/10.1007/s12013-016-0756-3

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  • DOI: https://doi.org/10.1007/s12013-016-0756-3

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