Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes.
Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes.
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DOI：
10.7554/elife.01133
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发表时间：
2013-11-05
期刊：
影响因子：
7.7
通讯作者：
Nasmyth K
中科院分区：
文献类型：
--
作者：
Rattani A;Wolna M;Ploquin M;Helmhart W;Morrone S;Mayer B;Godwin J;Xu W;Stemmann O;Pendas A;Nasmyth K
精确的染色体分离依赖于内聚解析和着丝粒-微管相互作用（K-纤维）之间的协调，这是一个由纺锤体组装检查点（SAC）调节的过程。如何协调这些不同的进程仍不清楚。我们发现，在哺乳动物卵母细胞Shugoshin-like蛋白2（Sgol 2）除了保护粘连蛋白，起着重要的作用，在关闭SAC，在促进大会和双取向的二价体减数分裂I纺锤体，在促进K-纤维的形成和限制二价拉伸。Sgol 2保护粘附素的能力取决于其与PP 2A的相互作用，其沉默SAC的能力也是如此，后者通过直接结合Mad 2介导。相反，其对二价拉伸和K-纤维形成的作用独立于PP 2A，并分别通过募集MCAK和抑制Aurora C激酶活性介导。由于其多重相互作用，Sgol 2连接了许多对可靠的染色体分离至关重要的过程。http://dx.doi.org/10.7554/eLife.01133.001人类的生殖细胞--卵子和精子--是通过一个叫做减数分裂的过程产生的。这意味着卵巢或睾丸中的“父”细胞经历两个细胞分裂阶段：它首先分裂为两个细胞，然后再次分裂产生四个“子”细胞。减数分裂的一个关键部分是确保每个子细胞的染色体数量是母细胞的一半。在第一轮减数分裂之前，母细胞中的染色体被复制，以产生足够的染色体供四个子细胞使用。这些染色体在子细胞之间的分布是由作用在它们上的相反的力决定的。在复制过程中产生的成对的相同染色体通过蛋白质胶水结合在一起，而微管附着在一种叫做纺锤体的结构上，纺锤体在细胞的两端有两极，微管试图将这些成对的染色体分开。Rattani等人现在表明，一种名为shugoshin-like 2（Sgol 2）的蛋白质在第一轮分裂后参与将相同的染色体对保持在一起，其作用比以前意识到的更大。Sgol 2还执行其他三个功能：它有助于在分裂前排列染色体，据认为，它促进了将微管连接到染色体上的K纤维的形成;它关闭了监测染色体排列和微管连接的检查点;它调节了参与该过程的许多酶。还鉴定了允许Sgol 2在减数分裂中执行这些不同功能的特定相互作用。因此，Rattani等人表明，在整个减数分裂过程中连接如此多的基本过程，Sgol 2似乎在决定细胞分裂时染色体的命运方面具有关键（如果不是唯一的话）作用。DOI：http://dx.doi.org/10.7554/eLife.01133.002网站
Accurate chromosome segregation depends on coordination between cohesion resolution and kinetochore-microtubule interactions (K-fibers), a process regulated by the spindle assembly checkpoint (SAC). How these diverse processes are coordinated remains unclear. We show that in mammalian oocytes Shugoshin-like protein 2 (Sgol2) in addition to protecting cohesin, plays an important role in turning off the SAC, in promoting the congression and bi-orientation of bivalents on meiosis I spindles, in facilitating formation of K-fibers and in limiting bivalent stretching. Sgol2’s ability to protect cohesin depends on its interaction with PP2A, as is its ability to silence the SAC, with the latter being mediated by direct binding to Mad2. In contrast, its effect on bivalent stretching and K-fiber formation is independent of PP2A and mediated by recruitment of MCAK and inhibition of Aurora C kinase activity respectively. By virtue of its multiple interactions, Sgol2 links many of the processes essential for faithful chromosome segregation. DOI: http://dx.doi.org/10.7554/eLife.01133.001 Human reproductive cells—eggs and sperm—are produced through a process called meiosis. This means a ‘parent’ cell in the ovaries or testes undergoes two stages of cell division: it first divides into two cells, which then divide again to produce four ‘daughter’ cells. A crucial part of meiosis is ensuring that each daughter cell has half the number of chromosomes that the parent cell did. Before the first round of meiosis, the chromosomes in the parent cell are copied to produce enough chromosomes for the four daughter cells. The distribution of these chromosomes between the daughter cells is determined by the opposing forces acting on them. The pairs of identical chromosomes produced during the copying process are held together by a proteinaceous glue, while microtubules attached to a structure called the spindle—which has poles at opposite ends of the cell—try to pull these pairs of chromosomes apart. Rattani et al. now show that a protein called shugoshin-like 2 (Sgol2), which is involved in holding pairs of identical chromosomes together after the first round of division, has a bigger role than was previously realised. Sgol2 performs three other functions: it helps to align the chromosomes prior to division by, it is thought, facilitating the formation of the K-fibers that attach the microtubules to the chromosomes; it turns off the checkpoint that monitors the alignment of the chromosomes and the attachment of the microtubules; and it regulates a number of the enzymes involved in the process. The specific interactions that allow Sgol2 to perform these diverse functions in meiosis were also identified. Thus, Rattani et al. show that in linking so many essential processes throughout meiosis, Sgol2 appears to have a key, if not unique, role in determining the fate of chromosomes as cells divide. DOI: http://dx.doi.org/10.7554/eLife.01133.002