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HSP70 regulates the function of mitotic centrosomes

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Abstract

To establish a functional bipolar mitotic spindle, the centrosome expands and matures, acquiring enhanced activities for microtubule (MT) nucleation and assembly at the onset of mitosis. However, the regulatory mechanisms of centrosome maturation and MT assembly from the matured centrosome are largely unknown. In this study, we showed that heat shock protein (HSP) 70 considerably accumulates at the mitotic centrosome during prometaphase to metaphase and is required for bipolar spindle assembly. Inhibition or depletion of HSP70 impaired the function of mitotic centrosome and disrupted MT nucleation and polymerization from the spindle pole, and may thus result in formation of abnormal mitotic spindles. In addition, HSP70 may associate with NEDD1 and γ-tubulin, two pericentriolar material (PCM) components essential for centrosome maturation and MT nucleation. Loss of HSP70 function disrupted the interaction between NEDD1 and γ-tubulin, and reduced their accumulation at the mitotic centrosome. Our results thus demonstrate a role for HSP70 in regulating centrosome integrity during mitosis, and indicate that HSP70 is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle.

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Acknowledgments

The authors thank the Core Facility of the Institute of Cellular and Organismic Biology, Academia Sinica, for their assistance with confocal microscopy and image analysis. This work was supported by grants from Academia Sinica and the Ministry of Science and Technology (NSC 102-2320-B-001-023-MY3), Taiwan.

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    1. Department of Life Science, National Taiwan University, Taipei, Taiwan

      Chieh-Ting Fang & Ling-Huei Yih

    2. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan

      Chieh-Ting Fang, Hsiao-Hui Kuo, Tiffany S. Pan, Fu-Chi Yu & Ling-Huei Yih

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    C.-T. Fang and H.-H. Kuo contribute equally.

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    Fang, CT., Kuo, HH., Pan, T.S. et al. HSP70 regulates the function of mitotic centrosomes. Cell. Mol. Life Sci. 73, 3949–3960 (2016). https://doi.org/10.1007/s00018-016-2236-8

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