Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Miyagi, Japan.
Cell Mol Life Sci. 2013 Feb;70(4):559-79. doi: 10.1007/s00018-012-1057-7. Epub 2012 Jul 4.
Interaction of microtubules with kinetochores is fundamental to chromosome segregation. Kinetochores initially associate with lateral surfaces of microtubules and subsequently become attached to microtubule ends. During these interactions, kinetochores can move by sliding along microtubules or by moving together with depolymerizing microtubule ends. The interplay between kinetochores and microtubules leads to the establishment of bi-orientation, which is the attachment of sister kinetochores to microtubules from opposite spindle poles, and subsequent chromosome segregation. Molecular mechanisms underlying these processes have been intensively studied over the past 10 years. Emerging evidence suggests that the KNL1-Mis12-Ndc80 (KMN) network plays a central role in connecting kinetochores to microtubules, which is under fine regulation by a mitotic kinase, Aurora B. However, a growing number of additional molecules are being shown to be involved in the kinetochore-microtubule interaction. Here I overview the current range of regulatory mechanisms of the kinetochore-microtubule interaction, and discuss how these multiple molecules contribute cooperatively to allow faithful chromosome segregation.
微管与动粒的相互作用是染色体分离的基础。动粒最初与微管的侧面结合,随后与微管末端结合。在这些相互作用过程中,动粒可以通过在微管上滑动或与解聚的微管末端一起移动来移动。动粒和微管之间的相互作用导致双定向的建立,即姐妹动粒附着在来自纺锤体两极的微管上,随后发生染色体分离。在过去的 10 年中,人们对这些过程的分子机制进行了深入研究。新出现的证据表明,KNL1-Mis12-Ndc80(KMN)网络在将动粒连接到微管中起着核心作用,这一过程受到有丝分裂激酶 Aurora B 的精细调节。然而,越来越多的其他分子被证明参与了动粒-微管相互作用。在这里,我概述了目前动粒-微管相互作用的调节机制范围,并讨论了这些多种分子如何协同作用以确保染色体的准确分离。