Agnati Luigi F, Guidolin Diego, Carone Chiara, Dam Mauro, Genedani Susanna, Fuxe Kjell
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Brain Res Rev. 2008 Aug;58(2):379-99. doi: 10.1016/j.brainresrev.2007.11.002. Epub 2007 Nov 26.
The central nervous system (CNS) is a nested network at all levels of its organization. In particular, neuronal cellular networks (the neuronal circuits), interconnected to form neuronal systems, are formed by neurons, which operate thanks to their molecular networks. Proteins are the main components of the molecular networks and via protein-protein interactions can be assembled in multimeric complexes, which can work as micro-devices. On this basis, we have introduced the term "fractal logic" to describe networks of networks where at the various levels of the nested organization the same rules (logic) to perform operations are used. If this assumption is true, the description of the information handling at one of the nested levels sheds light on the way in which similar operations are carried out at other levels. This conceptual frame has been used to deduce from some features of neuronal networks the features of the molecular networks as far as modes for inter-node communication and their architecture. It should be noted that these features are such to allow a highly regulated cross-talk between signalling pathways, hence preserving selectivity and privacy. To investigate these aspects, the protein-protein interactions in beta2 Adrenergic Receptor (beta2AR) and Epidermal growth factor receptor (EGFR) signalling pathways have been analysed. The presence of disordered sequences in interacting domains can favour via the "fly-casting mechanism" protein-protein interactions, in addition it favours an induced-fitting rather than a lock-key type of interactions. Thus, by means of a computer assisted analysis the presence of disorder sequences in the main streams of the molecular networks that have beta2AR and EGFR as input proteins leading to MAP kinase activation has been evaluated.
中枢神经系统(CNS)在其组织的各个层面都是一个嵌套网络。特别是,相互连接形成神经元系统的神经元细胞网络(神经元回路)由神经元构成,而神经元借助其分子网络发挥作用。蛋白质是分子网络的主要组成部分,通过蛋白质 - 蛋白质相互作用可组装成多聚体复合物,这些复合物可作为微型装置发挥作用。在此基础上,我们引入了“分形逻辑”一词来描述网络的网络,即在嵌套组织的各个层面使用相同的规则(逻辑)来执行操作。如果这一假设成立,那么对嵌套层面之一的信息处理描述将有助于揭示其他层面进行类似操作的方式。这个概念框架已被用于从神经元网络的某些特征推断分子网络在节点间通信模式及其架构方面的特征。应当指出,这些特征能够实现信号通路之间高度调控的相互作用,从而保持选择性和隐私性。为了研究这些方面,我们分析了β2肾上腺素能受体(beta2AR)和表皮生长因子受体(EGFR)信号通路中的蛋白质 - 蛋白质相互作用。相互作用结构域中无序序列的存在可通过“抛锚机制”促进蛋白质 - 蛋白质相互作用,此外还有利于诱导契合而非锁钥型相互作用。因此,通过计算机辅助分析,我们评估了以beta2AR和EGFR作为输入蛋白导致MAP激酶激活的分子网络主流中无序序列的存在情况。