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光遗传学调控揭示细胞收缩信号网络中 Rho 放大依赖性动力学。

Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network.

机构信息

Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany; Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.

Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.

出版信息

Cell Rep. 2020 Dec 1;33(9):108467. doi: 10.1016/j.celrep.2020.108467.

Abstract

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

摘要

局部细胞收缩脉冲在组织和细胞形态发生中起着重要作用。在这里,我们改进了一种化学-光遗传学方法,并应用它来研究产生这些脉冲的信号网络。我们使用这些测量结果来推导出并参数化一个描述时间信号网络动态的常微分方程系统。分支分析和数值模拟预测,振荡系统动力学强烈依赖于 GEF-H1 的浓度,GEF-H1 是一种 Lbc 型 RhoGEF,介导 Rho 活性的正反馈放大。通过在单个活细胞中光遗传学调节有效 GEF-H1 浓度,实验验证了这一预测。数值模拟表明,在低 GEF-H1 浓度下,脉冲幅度对肌球蛋白组分的外部输入最敏感,而脉冲宽度与 GEF-H1 扩散有关。我们的研究提供了一个理论框架,用于解释局部细胞收缩脉冲的出现及其受生化和机械信号的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4c1/7710677/2ffda6a719ba/fx1.jpg

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