Regulated Activation of the PAR Polarity Network Ensures a Timely and Specific Response to Spatial Cues
Regulated Activation of the PAR Polarity Network Ensures a Timely and Specific Response to Spatial Cues
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DOI：
10.1016/j.cub.2019.04.058
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发表时间：
2019-06-17
期刊：
影响因子：
9.2
通讯作者：
Goehring, Nathan W.
中科院分区：
文献类型：
--
作者：
Reich, Jacob D.;Hubatsch, Lars;Goehring, Nathan W.
细胞是如何在正确的时间并对正确的线索做出反应的？在C.在线虫受精卵中，极化的时间和几何形状依赖于一个单一的主导线索-精子中心体-它在减数分裂结束时成熟并指定新生的后部。极化需要保守的PAR蛋白，它在合子中指定极性，准备响应中心体。然而，PAR蛋白如何以及何时达到这种非极化但响应性的状态尚不清楚。我们表明，卵母细胞成熟启动一个受精独立的PAR激活程序。PAR蛋白最初没有能力去成熟，但随着卵母细胞成熟逐渐获得这种能力。令人惊讶的是，这个程序允许对称性破坏，即使在未受精的卵母细胞缺乏中心体。因此，如果PAR蛋白能对多种极化信号作出反应，那么对中心体的特异性是如何实现的呢？特异性由Polo样和Aurora激酶（C. elegans），其在PAR网络的激活中施加延迟，使得其与中心体线索的成熟一致。这种延迟通过非中心体线索抑制极化，否则会触发过早极化和多个或反向极性域。总之，这些研究结果确定了一个监管程序，强制执行适当的极化同步PAR网络激活与细胞周期进程，从而确保PAR蛋白特异性地响应正确的线索。极性网络活动的时间控制很可能是一种常见的策略，以确保强大的，动态的，和特定的极化，以响应发展部署的线索。
How do cells polarize at the correct time and in response to the correct cues? In the C. elegans zygote, the timing and geometry of polarization rely on a single dominant cue-the sperm centrosome-that matures at the end of meiosis and specifies the nascent posterior. Polarization requires that the conserved PAR proteins, which specify polarity in the zygote, be poised to respond to the centrosome. Yet, how and when PAR proteins achieve this unpolarized, but responsive, state is unknown. We show that oocyte maturation initiates a fertilization-independent PAR activation program. PAR proteins are initially not competent to polarize but gradually acquire this ability following oocyte maturation. Surprisingly, this program allows symmetry breaking even in unfertilized oocytes lacking centrosomes. Thus, if PAR proteins can respond to multiple polarizing cues, how is specificity for the centrosome achieved? Specificity is enforced by Polo-like and Aurora kinases (PLK-1 and AIR-1 in C. elegans), which impose a delay in the activation of the PAR network so that it coincides with maturation of the centrosome cue. This delay suppresses polarization by non-centrosomal cues, which can otherwise trigger premature polarization and multiple or reversed polarity domains. Taken together, these findings identify a regulatory program that enforces proper polarization by synchronizing PAR network activation with cell cycle progression, thereby ensuring that PAR proteins respond specifically to the correct cue. Temporal control of polarity network activity is likely to be a common strategy to ensure robust, dynamic, and specific polarization in response to developmentally deployed cues.