title: HSP70 regulates the function of mitotic centrosomes.
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.
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan.|Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan.
authors.forename: Chieh-Ting
authors.initials: CT
authors.lastname: Fang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan.
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Kuo
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan.
authors.forename: Tiffany S
authors.initials: TS
authors.lastname: Pan
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan.
authors.forename: Fu-Chi
authors.initials: FC
authors.lastname: Yu
authors.affiliation: Department of Life Science, National Taiwan University, Taipei, Taiwan. lhyih@gate.sinica.edu.tw.|Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 115, Taiwan. lhyih@gate.sinica.edu.tw.
authors.forename: Ling-Huei
authors.initials: LH
authors.lastname: Yih
mesh_terms: D018385:Centrosome / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D058105:Polymerization; D011485:Protein Binding; D064047:Spindle Poles / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; C509189:NEDD1 protein, human; D014404:Tubulin
keywords: HSP70; Microtubule nucleation; Microtubule polymerization; Mitotic spindle; Spindle pole