RESUMO
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.
Assuntos
Hipocampo/citologia , Neurônios/fisiologia , Transdução de Sinais , Algoritmos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Retroalimentação Fisiológica , Ácido Glutâmico/metabolismo , Hipocampo/fisiologia , Homeostase , Ligantes , Potenciação de Longa Duração , Mamíferos , Matemática , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Neurológicos , Plasticidade Neuronal , Norepinefrina/metabolismo , Proteína Quinase C/metabolismo , Receptores de AMPA/metabolismo , Software , Biologia de SistemasRESUMO
CEACAM1 is a signal-regulating, homophilic cell adhesion receptor system expressed in epithelia, vessel endothelia, and leukocytes. Here, we demonstrate that CEACAM1 is expressed also in PC12 cells, both as the common transmembrane isoforms, CEACAM1-L and CEACAM1-S, and as a novel, secreted, differentially spliced isoform. CEACAM1 can have both positive and negative effects on cell signaling. In an attempt to explain this dual behavior, we have initiated computational analysis of the signal-regulating effects of CEACAM1. This suggests that CEACAM1 can exert its signal-regulating activities by discriminating between binding of Src kinases and SHP phosphatases, respectively. Major factors that regulate this discrimination are the expression levels and expression ratios of transmembrane CEACAM1-L and CEACAM1-S, the concentration of secreted CEACAM1, and homophilic binding of CEACAM1 presented by neighboring cells.
