@article{f1d9d7482f3543368c5b1ab2bbadf020,
title = "The γ-tubulin-specific inhibitor gatastatin reveals temporal requirements of microtubule nucleation during the cell cycle",
abstract = "Inhibitors of microtubule (MT) assembly or dynamics that target α/β-tubulin are widely exploited in cancer therapy and biological research. However, specific inhibitors of the MT nucleator γ-tubulin that would allow testing temporal functions of γ-tubulin during the cell cycle are yet to be identified. By evolving β-tubulin-binding drugs we now find that the glaziovianin A derivative gatastatin is a γ-tubulin-specific inhibitor. Gatastatin decreased interphase MT dynamics of human cells without affecting MT number. Gatastatin inhibited assembly of the mitotic spindle in prometaphase. Addition of gatastatin to preformed metaphase spindles altered MT dynamics, reduced the number of growing MTs and shortened spindle length. Furthermore, gatastatin prolonged anaphase duration by affecting anaphase spindle structure, indicating the continuous requirement of MT nucleation during mitosis. Thus, gatastatin facilitates the dissection of the role of γ-tubulin during the cell cycle and reveals the sustained role of γ-tubulin.",
author = "Takumi Chinen and Peng Liu and Shuya Shioda and Judith Pagel and Berati Cerikan and Lin, {Tien Chen} and Oliver Gruss and Yoshiki Hayashi and Haruka Takeno and Tomohiro Shima and Yasushi Okada and Ichiro Hayakawa and Yoshio Hayashi and Hideo Kigoshi and Takeo Usui and Elmar Schiebel",
note = "Funding Information: We thank U. J{\"a}kle for protein purification, the University of Colorado Boulder, protein expression facility, for the gift of human g-tubulin-expressing virus, A. Merdes (Centre de Recherche en Pharmacologie-Sant{\'e}) for the gift of GCP4 expressing plasmid, J. Ellenberg, L. Sironi (EMBL Heidelberg) and members of the ZMBH imaging facility for helpful suggestions for the analysis of EB3-EGFP-expressing HeLa cells. We thank S. Enya and R. Niwa for the help with the confocal microscopy analysis. For Xenopus experiments, we thank Y. Hao (ZMBH Heidelberg) for support with the egg extract preparations, and H. Yokoyama (Friedrich Miescher Laboratory T{\"u}bingen) for help with the quantification. We thank Heidelberg University-Nikon Imaging Center for the SIM analysis. We are grateful to A.A. Hyman and J. Ellenberg for HeLa cell lines. S. Hata and F.G. Agircan are acknowledged for helpful suggestions. We are also thankful to I. Hagan (Cancer Research UK Manchester Institute) for comments on the manuscript. This work was supported by a Grant-in-Aid for Scientific Research on the Innovative Area {\textquoteleft}Chemical Biology of Natural Products{\textquoteright} and {\textquoteleft}Spying Minority in Biological Phenomena{\textquoteright} from The Ministry of Education, Culture, Sports, Science and Technology, Japan, by Japan Society for the Promotion of Science (JSPS), KAKENHI including a Grant-in-Aid for Scientific Research 23390029, 24659092, 25113723, 25293046 and Platform for Drug Discovery, by a Grant-in-Aid for JSPS Fellows, and by the strategic programmes for R&D (President{\textquoteright}s discretionary fund) of RIKEN. The work of E.S. was supported by a grant from the Deutsche Forschungsgemeinschaft Schi295/4-2. T.C. was supported by the Uehara memorial foundation and JSPS Postdoctoral Fellowships for Research Abroad. T.S. was supported by the Special Postdoctoral Researcher (SPDR) programme in RIKEN. J.P., T.-c.L., P.L. and B.C. are members of the International Graduate School HBIGS.",
year = "2015",
month = oct,
day = "27",
doi = "10.1038/ncomms9722",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}
