The polarity protein Baz forms a platform for the centrosome orientation during asymmetric stem cell division in the Drosophila male germline.
The polarity protein Baz forms a platform for the centrosome orientation during asymmetric stem cell division in the Drosophila male germline.
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DOI：
10.7554/elife.04960
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发表时间：
2015-03-20
期刊：
影响因子：
7.7
通讯作者：
Yamashita YM
中科院分区：
文献类型：
--
作者：
Inaba M;Venkei ZG;Yamashita YM
许多干细胞不对称分裂，以平衡自我更新与分化。不对称细胞分裂（ACD）的本质是细胞的极化和随后的分裂，导致细胞/细胞外组分的不均等区室化，从而赋予子细胞不同的细胞命运。因为在建立细胞极性之前过早的细胞分裂会导致ACD失败，所以这两个过程必须紧密耦合;然而，对潜在的机制知之甚少。在果蝇雄性生殖系干细胞中，ACD是通过刻板的中心体定位制备的。中心体定向检查点（COC）进一步通过防止中心体错误定向后的有丝分裂来确保ACD。在这项研究中，我们表明，Bazooka（巴兹）提供了一个平台，正确的中心体方向和巴兹中心体协会是由COC监测的关键事件。我们的工作为理解细胞如何识别正确的细胞极性以确保生产性ACD提供了基础。DOI：http://dx.doi.org/10.7554/eLife.04960.001动物身体的组织是由最初来自干细胞的细胞构建的。每一个干细胞都可以分裂并产生另一个干细胞和一个细胞，后者将成为一种更特殊的细胞，如神经细胞、肌肉细胞或精子细胞。如果这种不对称的细胞分裂被破坏，它可能导致发育障碍和癌症等疾病。当细胞分裂时，一种被称为纺锤体的结构将染色体的拷贝分成两个新形成的细胞。纺锤体由长的蛋白质丝组成，这些蛋白质丝从两个被称为中心体的较小结构延伸出来，中心体位于细胞的相对两侧。这些中心体的位置决定了纺锤体的方向，而纺锤体的方向又决定了细胞分裂发生的平面。因此，需要以特定方向分裂的细胞必须具有确保其中心体正确定位的机制。然而，这种机制的存在一直未被充分探索，并且仍然不清楚中心体的排列是如何控制的。Inaba等人分析了雄性果蝇中的干细胞如何不对称地分裂，形成一个干细胞和第二个细胞，然后发育成精子。实验表明，一种名为Bazooka（或简称Baz）的蛋白质在细胞开始分裂之前与中心体密切相关。许多其他动物，如人类和蠕虫，都有与Bazooka密切相关的蛋白质，这是不对称细胞分裂所必需的。当Inaba等人降低果蝇细胞中Bazooka蛋白的水平时，大量这些细胞最终具有不正确排列的中心体。结果，这些细胞的纺锤体也被错误地定向。这些发现表明，当中心体被正确定向时，火箭筒和中心体之间的相互作用通知细胞。然而，需要进一步的工作来确定Bazooka如何控制不对称细胞分裂的细节。DOI：http://dx.doi.org/10.7554/eLife.04960.002网站
Many stem cells divide asymmetrically in order to balance self-renewal with differentiation. The essence of asymmetric cell division (ACD) is the polarization of cells and subsequent division, leading to unequal compartmentalization of cellular/extracellular components that confer distinct cell fates to daughter cells. Because precocious cell division before establishing cell polarity would lead to failure in ACD, these two processes must be tightly coupled; however, the underlying mechanism is poorly understood. In Drosophila male germline stem cells, ACD is prepared by stereotypical centrosome positioning. The centrosome orientation checkpoint (COC) further serves to ensure ACD by preventing mitosis upon centrosome misorientation. In this study, we show that Bazooka (Baz) provides a platform for the correct centrosome orientation and that Baz-centrosome association is the key event that is monitored by the COC. Our work provides a foundation for understanding how the correct cell polarity may be recognized by the cell to ensure productive ACD. DOI: http://dx.doi.org/10.7554/eLife.04960.001 The tissues of an animal's body are built from cells that are originally derived from stem cells. Each stem cell can divide and give rise to another stem cell and a cell that will become a more specific type of cell—such as a nerve cell, muscle cell, or sperm cell. If this asymmetric cell division is disrupted, it can result in developmental disorders and diseases such as cancer. When a cell divides, a structure known as the spindle separates the copies of the chromosomes into the two newly formed cells. The spindle consists of long protein filaments that extend from two smaller structures known as centrosomes, which are found at opposite sides of the cell. The position of these centrosomes governs the orientation of the spindle, which in turn determines the plane in which cell division takes place. Thus, cells that need to divide with a certain orientation must have a mechanism that ensures that their centrosomes are correctly positioned. However, the existence of such a mechanism has been underexplored, and it remains unclear how the alignment of the centrosomes is controlled. Inaba et al. analyzed how stem cells in the male fruit fly divide asymmetrically to form one stem cell and second cell that develops into sperm. The experiments revealed that a protein called Bazooka (or Baz for short) closely associates with the centrosomes just before the cells start to divide. Many other animals—such as humans and worms—have proteins that are closely related to Bazooka, which are needed for asymmetric cell divisions. When Inaba et al. reduced the levels of the Bazooka protein in the fruit fly cells, a large number of these cells ended up with centrosomes that were incorrectly aligned. As a result, these cells' spindles were also oriented incorrectly. These findings suggest that the interactions between Bazooka and the centrosomes inform a cell when the centrosomes are correctly orientated. However, further work will be required to determine the details of how Bazooka controls asymmetric cell divisions. DOI: http://dx.doi.org/10.7554/eLife.04960.002