SCWISh network is essential for survival under mechanical pressure
SCWISh network is essential for survival under mechanical pressure
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DOI：
10.1073/pnas.1711204114
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发表时间：
2017-12-19
影响因子：
11.1
通讯作者：
Hallatschek, Oskar
中科院分区：
文献类型：
--
作者：
Delarue, Morgan;Poterewicz, Gregory;Hallatschek, Oskar
在受限环境中增殖的细胞建立机械压缩应力。例如，机械压力出现在自然空间有限的肿瘤环境中。然而，人们对细胞如何感知和响应机械压缩知之甚少。我们开发了微流控生物反应器，使调查的影响，压应力的生长的遗传听话的模式生物酿酒酵母。我们使用这个系统来确定，压缩应力部分通过由粘蛋白Msb 2和细胞壁蛋白Sho 1组成的模块来感知，它们一起作为芽殖酵母中两个主要的细胞壁传感途径之一的传感器模块。该信号通过MAPKKK激酶Ste 11传递。因此，我们将这种机械敏感途径称为“SMuSh”途径，即Ste 11通过粘蛋白/Sho 1途径。SMuSh通路延迟细胞处于细胞周期的G1期，并提高细胞对生长诱导的压力的反应。我们还发现，细胞壁完整性（CWI）途径有助于对机械压应力的反应。这些后一结果在Mishra等人的补充实验中得到证实[Mishra R等人（2017）Proc Natl Acad Sci USA，10.1073/pnas. 1709079114]。当SMuSh和CWI途径都被删除时，细胞不能适应压缩应力，并且当在限制中生长时，所有细胞在相对低的压力下裂解。因此，我们定义了一个在压力下生长的细胞生存所必需的网络。我们将这种机械感觉系统称为SCWISh（通过CWI和SMuSh生存）网络。
Cells that proliferate within a confined environment build up mechanical compressive stress. For example, mechanical pressure emerges in the naturally space-limited tumor environment. However, little is known about how cells sense and respond to mechanical compression. We developed microfluidic bioreactors to enable the investigation of the effects of compressive stress on the growth of the genetically tractable model organism Saccharomyces cerevisiae. We used this system to determine that compressive stress is partly sensed through a module consisting of the mucin Msb2 and the cell wall protein Sho1, which act together as a sensor module in one of the two major osmosensing pathways in budding yeast. This signal is transmitted via the MAPKKK kinase Ste11. Thus, we term this mechanosensitive pathway the "SMuSh" pathway, for Ste11 through Mucin/Sho1 pathway. The SMuSh pathway delays cells in the G1 phase of the cell cycle and improves cell survival in response to growth-induced pressure. We also found that the cell wall integrity (CWI) pathway contributes to the response to mechanical compressive stress. These latter results are confirmed in complimentary experiments in Mishra et al. [Mishra R, et al. (2017) Proc Natl Acad Sci USA, 10.1073/pnas. 1709079114]. When both the SMuSh and the CWI pathways are deleted, cells fail to adapt to compressive stress, and all cells lyse at relatively low pressure when grown in confinement. Thus, we define a network that is essential for cell survival during growth under pressure. We term this mechanosensory system the SCWISh (survival through the CWI and SMuSh) network.