Hersen Pascal, McClean Megan N, Mahadevan L, Ramanathan Sharad
FAS Center for Systems Biology and School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 2008 May 20;105(20):7165-70. doi: 10.1073/pnas.0710770105. Epub 2008 May 14.
Signaling pathways relay information about changes in the external environment so that cells can respond appropriately. How much information a pathway can carry depends on its bandwidth. We designed a microfluidic device to reliably change the environment of single cells over a range of frequencies. Using this device, we measured the bandwidth of the Saccharomyces cerevisiae signaling pathway that responds to high osmolarity. This prototypical pathway, the HOG pathway, is shown to act as a low-pass filter, integrating the signal when it changes rapidly and following it faithfully when it changes more slowly. We study the dependence of the pathway's bandwidth on its architecture. We measure previously unknown bounds on all of the in vivo reaction rates acting in this pathway. We find that the two-component Ssk1 branch of this pathway is capable of fast signal integration, whereas the kinase Ste11 branch is not. Our experimental techniques can be applied to other signaling pathways, allowing the measurement of their in vivo kinetics and the quantification of their information capacity.
信号通路传递有关外部环境变化的信息,以便细胞能够做出适当反应。一条通路能够携带的信息量取决于其带宽。我们设计了一种微流控装置,以在一系列频率范围内可靠地改变单细胞的环境。使用该装置,我们测量了酿酒酵母对高渗透压作出反应的信号通路的带宽。这条典型的通路,即高渗甘油(HOG)通路,被证明起到低通滤波器的作用,在信号快速变化时对其进行整合,并在信号变化较慢时忠实地跟踪它。我们研究了该通路带宽对其架构的依赖性。我们测量了该通路中所有体内反应速率的先前未知界限。我们发现该通路的双组分Ssk1分支能够快速进行信号整合,而激酶Ste11分支则不能。我们的实验技术可应用于其他信号通路,从而能够测量它们的体内动力学并量化其信息容量。