Connecting with Ska, a key complex at the kinetochore-microtubule interface.
Connecting with Ska, a key complex at the kinetochore-microtubule interface.
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DOI：
10.1038/emboj.2009.124
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发表时间：
2009-05-20
期刊：
影响因子：
11.4
通讯作者：
DeLuca, Jennifer G.
中科院分区：
文献类型：
--
作者：
Guimaraes, Geoffrey J.;DeLuca, Jennifer G.
有丝分裂过程中染色体高度协调的运动取决于微管和动粒之间稳定连接的形成。动粒如何产生这些连接以利用动态微管正端产生的力仍然未知。最近的三项研究在这方面取得了重大进展，确定了与着丝粒相关的 Ska（纺锤体和着丝粒相关）复合体的第三个组成部分，并证明该复合体是在人类细胞有丝分裂过程中产生稳定的着丝粒-微管附着所必需的。有丝分裂中的染色体排列和分离需要纺锤体微管和着丝粒之间强大而灵活的连接。主要的难题是动粒如何产生和维持与微管正端的附着的分子细节，微管正端不断获得和失去微管蛋白二聚体。在出芽酵母中，沿着有丝分裂纺锤体微管定位的 Dam1 复合体需要形成稳定的着丝粒-微管附着物（Jones 等，2001）。 Dam1 复合体已被提议通过与动粒定位的 Ndc80 复合体合作来生成这些附着物（Shang 等人，2003）（图 1）。 Dam1 复合物在体外在微管上形成环和非环寡聚体，两者都能够追踪解聚微管正端（Gardner 和 Odde，2008 年综述），这意味着这些复合物可能能够将微管与细胞中的动粒连接起来。然而，尽管进行了彻底的搜索，但在高等真核生物中尚未发现 Dam1 同源物。 Ndc80 复合物（存在于所有真核生物中）可以独立形成这些连接，因为该复合物对于细胞中动粒-微管附着至关重要（Ciferri 等人，2007 年综述），并且与 Dam1 类似，可以与动态微管正端结合并跟踪（Powers 等人，2009）。然而，许多额外的蛋白质定位于有丝分裂细胞中的动粒-微管界面，并且可能需要其他成分来形成染色体双向取向所需的功能连接。最近的三篇论文（其中两篇发表在本期《EMBO 杂志》上）说明了这一点：Nigg、Buchholz 和 Cheeseman 小组都鉴定了 Ska 复合体的一种新成分，并证明该复合体是在人类细胞中形成稳定的动粒-微管附着所必需的（Gaitanos 等，2009；Theis 等，2009；Welburn 等，2009）。
The highly orchestrated movements of chromosomes during mitosis depend on the formation of stable connections between microtubules and kinetochores. How kinetochores generate these linkages to harness the forces produced by dynamic microtubule plus-ends remains unknown. Three recent studies make significant progress on this front, by identifying a third component of the kinetochore-associated Ska (spindle and kinetochore associated) complex and demonstrating that the complex is required to generate stable kinetochore–microtubule attachments during mitosis in human cells.Chromosome alignment and segregation in mitosis requires strong yet flexible connections between spindle microtubules and kinetochores. Major puzzles are the molecular details of how kinetochores generate and maintain attachments to microtubule plus-ends that are continually gaining and losing tubulin dimers. In budding yeast, the Dam1 complex, which localizes along mitotic spindle microtubules, is required to form stable kinetochore–microtubule attachments (Jones et al, 2001). The Dam1 complex has been proposed to generate these attachments by partnering with the kinetochore-localized Ndc80 complex (Shang et al, 2003)(Figure 1). Dam1 complexes form rings and non-ring oligomers on microtubules in vitro, both of which are able to track with depolymerizing microtubule plus-ends (reviewed in Gardner and Odde, 2008), implying that these complexes may be competent to link microtubules to kinetochores in cells. Despite thorough searches, however, no Dam1 homologous have been identified in higher eukaryotes. The Ndc80 complex (which is present in all eukaryotes) may independently form these linkages, as this complex is essential for kinetochore–microtubule attachments in cells (reviewed in Ciferri et al, 2007) and similar to Dam1, can bind to and track with dynamic microtubule plus-ends (Powers et al, 2009). However, a host of additional proteins localize to the kinetochore–microtubule interface in mitotic cells, and it is likely that other components are needed to form the functional linkages required for chromosome bi-orientation. Three recent papers, two appearing in this issue of The EMBO Journal, illustrate this point: the Nigg, Buchholz and Cheeseman groups all identify a novel component of the Ska complex and demonstrate that the complex is required to form stable kinetochore–microtubule attachments in human cells (Gaitanos et al, 2009; Theis et al, 2009; Welburn et al, 2009).
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DOI：
10.1073/pnas.241417098
发表时间：
2001-11-20
影响因子：
11.1
作者：
Jones, MH;He, XW;Winey, M
通讯作者：
Winey, M
影响因子：
11.8
作者：
Welburn, Julie P. I.;Grishchuk, Ekaterina L.;Backer, Chelsea B.;Wilson-Kubalek, Elizabeth M.;Yates, John R., III;Cheeseman, Iain M.
通讯作者：
Cheeseman, Iain M.
影响因子：
3.3
作者：
Shang, C;Hazbun, TR;Barnes, G
通讯作者：
Barnes, G
影响因子：
11.4
作者：
Hanisch, Anja;Sillje, Herman H. W.;Nigg, Erich A.
通讯作者：
Nigg, Erich A.
影响因子：
11.4
作者：
Gaitanos, Thomas N.;Santamaria, Anna;Jeyaprakash, A. Arockia;Wang, Bin;Conti, Elena;Nigg, Erich A.
通讯作者：
Nigg, Erich A.