Nagano Seido, Sakurai Shunsuke
Department of Bioinformatics, Ritsumeikan University, 1-1-1 Nojihigashi, Shiga 525-8577, Japan.
Life Science Production Div., NOF Corporation, 5-10 Tokodai, Tsukuba 300-2635, Japan.
Phys Rev E Stat Nonlin Soft Matter Phys. 2013 Dec;88(6):062710. doi: 10.1103/PhysRevE.88.062710. Epub 2013 Dec 10.
We propose a new cellular dynamics scheme for the spontaneous cAMP oscillations in Dictyostelium discoideum. Our scheme seamlessly integrates both receptor dynamics and G-protein dynamics into our previously developed cellular dynamics scheme. Extensive computer simulation studies based on our new cellular dynamics scheme were conducted in mutant cells to evaluate the molecular network. The validity of our proposed molecular network as well as the controversial PKA-dependent negative feedback mechanism was supported by our simulation studies. Spontaneous cAMP oscillations were not observed in a single mutant cell. However, multicellular states of various mutant cells consistently initiated spontaneous cAMP oscillations. Therefore, cell-to-cell coordination via the cAMP receptor is essential for the robust initiation of spontaneous cAMP oscillations.
我们提出了一种针对盘基网柄菌中cAMP自发振荡的新细胞动力学方案。我们的方案将受体动力学和G蛋白动力学无缝整合到我们之前开发的细胞动力学方案中。基于我们的新细胞动力学方案，在突变细胞中进行了广泛的计算机模拟研究，以评估分子网络。我们的模拟研究支持了我们提出的分子网络以及有争议的PKA依赖性负反馈机制的有效性。在单个突变细胞中未观察到cAMP自发振荡。然而，各种突变细胞的多细胞状态一致地引发了cAMP自发振荡。因此，通过cAMP受体进行细胞间协调对于自发cAMP振荡的稳健启动至关重要。
