Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins CENP-E and MCAK.
Lateral to end-on conversion of chromosome-microtubule attachment requires kinesins CENP-E and MCAK.
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DOI：
10.1016/j.cub.2013.06.040
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发表时间：
2013-08-19
期刊：
影响因子：
9.2
通讯作者：
Draviam, Viji M.
中科院分区：
文献类型：
--
作者：
Shrestha, Roshan L.;Draviam, Viji M.
染色体与微管的正确连接对于染色体的准确分离至关重要。人类染色体最初附着在微管的侧壁上。随后，与侧壁的附着消失，与微管末端的附着(端对端附着)占主导地位。虽然在酵母菌中已知附件的侧向到末端的转换是通过多步骤过程进行的，但在人类中相同的转换步骤仍然未知。通过开发一种高分辨率成像分析来可视化横向到末端转换过程的中间步骤，我们表明，使横向结合的染色体及其微管末端相互靠近的机制对于正确的末端附着是必不可少的，因为横向附着的染色体很少分离。我们发现，端上转换需要(1)正端定向马达CENP-E将侧向动粒拴在微管壁上，(2)微管解聚器MCAK在部分端上附着形成后释放侧向附着的微管。通过发现CENP-E介导的壁拴系事件和MCAK介导的壁去除事件，我们建立了人类染色体-微管附着是通过一组确定性的顺序事件实现的，而不是随机地直接捕获微管末端。侧向动点很少分离，并逐渐转变为端-端动点，CENP-E是将动点连接到壁上所必需的，但不是微管末端，去除侧向附着的微管需要MCAK
Proper attachment of chromosomes to microtubules is crucial for the accurate segregation of chromosomes. Human chromosomes attach initially to lateral walls of microtubules. Subsequently, attachments to lateral walls disappear and attachments to microtubule ends (end-on attachments) predominate. While it is known in yeasts that lateral to end-on conversion of attachments occurs through a multistep process, equivalent conversion steps in humans remain unknown. By developing a high-resolution imaging assay to visualize intermediary steps of the lateral to end-on conversion process, we show that the mechanisms that bring a laterally bound chromosome and its microtubule end closer to each other are indispensable for proper end-on attachment because laterally attached chromosomes seldom detach. We show that end-on conversion requires (1) the plus-end-directed motor CENP-E to tether the lateral kinetochore onto microtubule walls and (2) the microtubule depolymerizer MCAK to release laterally attached microtubules after a partial end-on attachment is formed. By uncovering a CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event, we establish that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends. Lateral kinetochores seldom detach and are gradually converted to end-on kinetochores CENP-E is essential for tethering of kinetochores to walls but not microtubule ends MCAK is required for removing laterally attached microtubules
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DOI：
10.1083/jcb.201108147
发表时间：
2012-04-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Domnitz SB;Wagenbach M;Decarreau J;Wordeman L
通讯作者：
Wordeman L
影响因子：
21.3
作者：
Bakhoum, Samuel F.;Thompson, Sarah L.;Manning, Amity L.;Compton, Duane A.
通讯作者：
Compton, Duane A.
影响因子：
3.3
作者：
Kline-Smith, SL;Khodjakov, A;Walczak, CE
通讯作者：
Walczak, CE
影响因子：
16
作者：
Hunter, AW;Caplow, M;Howard, J
通讯作者：
Howard, J
影响因子：
11.4
作者：
Draviam, V. M.;Shapiro, I.;Sorger, P. K.
通讯作者：
Sorger, P. K.