The γ-tubulin-specific inhibitor gatastatin reveals temporal requirements of microtubule nucleation during the cell cycle

Takumi Chinen, Peng Liu, Shuya Shioda, Judith Pagel, Berati Cerikan, Tien-chen Lin, Oliver Gruss, Yoshiki Hayashi, Haruka Takeno, Tomohiro Shima, Yasushi Okada, Ichiro Hayakawa, Yoshio Hayashi, Hideo Kigoshi, Takeo Usui () and Elmar Schiebel ()
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Takumi Chinen: Graduate School of Life and Environmental Sciences, University of Tsukuba
Peng Liu: Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance
Shuya Shioda: Graduate School of Pure and Applied Sciences, University of Tsukuba
Judith Pagel: Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance
Berati Cerikan: Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance
Tien-chen Lin: Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance
Oliver Gruss: Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance
Yoshiki Hayashi: Tokyo University of Pharmacy and Life Sciences
Haruka Takeno: Tokyo University of Pharmacy and Life Sciences
Tomohiro Shima: Laboratory for Cell Polarity Regulation, RIKEN Quantitative Biology Center
Yasushi Okada: Laboratory for Cell Polarity Regulation, RIKEN Quantitative Biology Center
Ichiro Hayakawa: Graduate School of Natural Science and Technology, Okayama University
Yoshio Hayashi: Tokyo University of Pharmacy and Life Sciences
Hideo Kigoshi: Graduate School of Pure and Applied Sciences, University of Tsukuba
Takeo Usui: Graduate School of Life and Environmental Sciences, University of Tsukuba
Elmar Schiebel: Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9722

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