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

Author:

Ma'ayan Avi1234,Jenkins Sherry L.1234,Neves Susana1234,Hasseldine Anthony1234,Grace Elizabeth1234,Dubin-Thaler Benjamin1234,Eungdamrong Narat J.1234,Weng Gehzi1234,Ram Prahlad T.1234,Rice J. Jeremy1234,Kershenbaum Aaron1234,Stolovitzky Gustavo A.1234,Blitzer Robert D.1234,Iyengar Ravi1234

Affiliation:

1. Department of Pharmacology and Biological Chemistry Mount Sinai School of Medicine, New York, NY 10029, USA.

2. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.

3. Department of Biological Sciences, Columbia University, New York, NY 10029, USA.

4. Functional Genomics and Systems Biology, IBM T. J. Watson Research Center, Yorktown Heights, NY 10598, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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