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内吞作用和信号传导:Rab蛋白的竞争

Endocytosis and Signaling: Competition of Rab Proteins
课程网址: http://videolectures.net/eccs07_brusch_esc/  
主讲教师: Lutz Brusch
开课单位: 德累斯顿工业大学
开课时间: 2007-11-27
课程语种: 英语
中文简介:
内吞作用和信号传导密切相关。亚细胞区室的动态网络,称为内体,通过膜相关信号分子的摄取和转运,主动控制信号传播,振幅和定时。小GTP酶Rab5是蛋白质机器的中心组织者,在早期内体上组装,为隔室提供独特的身份,控制货物分类,运输和信号传导潜力。我们将实验和计算方法联系起来(I)揭示内吞途径功能和调节的基本设计原则,并(II)理解控制信号事件内体控制的分子联系。我们的方法考虑了新鉴定的Rab5效应子以及对新型内吞转运调节因子进行全基因组RNAi筛选的观点。我们开发并分析了内体组织者Rab4,Rab5和Rab7之间动力学相互作用的数学核心模型。从文献和FRAP实验估计模型参数的值。模型的模拟和分叉分析揭示了Rab5与Rab7优势的双稳态行为,其通过荧光活细胞成像数据中的单个内体的计算运动跟踪观察到,再现了从早期到晚期内体区室的控制和稳健转变。模拟的Rab5模块作为内吞途径的顺序组装的蓝图,由此为系统生物学贡献了重要的空间方面。我们的动力学模型解释了实验观察到的内体区室之间的转换,这是Rab蛋白之间货物调节竞争的结果。
课程简介: Endocytosis and signaling are tightly linked. A dynamic network of subcellular compartments, termed endosomes, actively controls signal propagation, amplitude and timing by uptake and transport of membrane-associated signaling molecules. The small GTPase Rab5 is the central organizer of the protein machinery that assembles on early endosomes, providing a unique identity to the compartment that controls cargo sorting, transport and signaling potential. We interlink experimental and computational approaches to (I) unravel the design principles underlying the function and regulation of the endocytic pathway and to (II) understand the molecular links that govern endosomal control of signaling events. Our approach takes into account both newly identified Rab5 effectors as well as the perspective of an on-going genome-wide RNAi screening for novel endocytic transport regulators. We develop and analyze a mathematical core model of the kinetic interactions between the endosomal organizers Rab4, Rab5 and Rab7. The values of the model parameters are estimated from literature and FRAP experiments. Simulations and bifurcation analysis of the model reveal bistable behavior of Rab5 versus Rab7 dominance that reproduces the controled and robust transition from early to late endosomal compartments as observed by means of computational motion tracking of individual endosomes in fluorescence live cell imaging data.The modeled Rab5 module serves as a blueprint for the sequential assembly of the endocytic pathway, therewith contributing an important spatial aspect to systems biology. Our kinetic model explains the experimentally observed transitions between endosomal compartments as the result of cargo-regulated competition between Rab proteins.
关 键 词: 内吞作用; 信号传导; 内体
课程来源: 视频讲座网
最后编审: 2020-06-29:cxin
阅读次数: 85