HSP70 regulates the function of mitotic centrosomes
HSP70 regulates the function of mitotic centrosomes
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DOI：
10.1007/s00018-016-2236-8
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发表时间：
2016-10-01
影响因子：
8
通讯作者：
Yih, Ling-Huei
中科院分区：
文献类型：
--
作者：
Fang, Chieh-Ting;Kuo, Hsiao-Hui;Yih, Ling-Huei
为了建立一个功能性的双极有丝分裂纺锤体，中心体扩张和成熟，在有丝分裂开始时获得微管（MT）成核和组装的增强活性。然而，中心体成熟和MT组装的调控机制在很大程度上是未知的。在这项研究中，我们发现，热休克蛋白（HSP）70相当大的积累在有丝分裂的中心体在前中期至中期，是所需的双极纺锤体组装。HSP 70的抑制或缺失会损害有丝分裂中心体的功能，破坏纺锤体极的MT成核和聚合，从而可能导致异常的有丝分裂纺锤体的形成。此外，HSP 70可能与NEDD 1和γ-微管蛋白，两个中心体成熟和MT成核所必需的中心粒周围物质（PCM）组分相关。HSP 70功能的丧失破坏了NEDD 1和γ-微管蛋白之间的相互作用，并减少了它们在有丝分裂中心体的积累。因此，我们的研究结果表明，热休克蛋白70在调节中心体的完整性在有丝分裂过程中的作用，并表明，热休克蛋白70是必要的功能有丝分裂中心体，支持组装的双极有丝分裂纺锤体的维护。
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 gamma-tubulin, two pericentriolar material (PCM) components essential for centrosome maturation and MT nucleation. Loss of HSP70 function disrupted the interaction between NEDD1 and gamma-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.