Formation of regulatory patterns during signal propagation in a Mammalian cellular network.
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.
Ma'ayan
Avi
A
Department of Pharmacology and Biological Chemistry Mount Sinai School of Medicine, New York, NY 10029, USA.
Jenkins
Sherry L
SL
Neves
Susana
S
Hasseldine
Anthony
A
Grace
Elizabeth
E
Dubin-Thaler
Benjamin
B
Eungdamrong
Narat J
NJ
Weng
Gehzi
G
Ram
Prahlad T
PT
Rice
J Jeremy
JJ
Kershenbaum
Aaron
A
Stolovitzky
Gustavo A
GA
Blitzer
Robert D
RD
Iyengar
Ravi
R
D000465:Algorithms; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D025461:Feedback, Physiological; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D006706:Homeostasis; D008024:Ligands; D017774:Long-Term Potentiation; D008322:Mammals; D008433:Mathematics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008959:Models, Neurological; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction; D012984:Software; D049490:Systems Biology
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D008024:Ligands; D018091:Receptors, AMPA; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009638:Norepinephrine