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Formation of Regulatory Patterns During Signal Propagation in a Mammalian Cellular Network

Science  12 Aug 2005:
Vol. 309, Issue 5737, pp. 1078-1083
DOI: 10.1126/science.1108876

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Abstract

We developed a model of 545 components (nodes) and 1259 interactions representing signaling pathways and cellular machines in the hippocampal CA1 neuron. Using graph theory methods, we analyzed ligand-induced signal flow through the system. Specification of input and output nodes allowed us to identify functional modules. Networking resulted in the emergence of regulatory motifs, such as positive and negative feedback and feedforward loops, that process information. Key regulators of plasticity were highly connected nodes required for the formation of regulatory motifs, indicating the potential importance of such motifs in determining cellular choices between homeostasis and plasticity.

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