RESUMEN
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.
Asunto(s)
Hipocampo/citología , Neuronas/fisiología , Transducción de Señal , Algoritmos , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Retroalimentación Fisiológica , Ácido Glutámico/metabolismo , Hipocampo/fisiología , Homeostasis , Ligandos , Potenciación a Largo Plazo , Mamíferos , Matemática , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Neurológicos , Plasticidad Neuronal , Norepinefrina/metabolismo , Proteína Quinasa C/metabolismo , Receptores AMPA/metabolismo , Programas Informáticos , Biología de SistemasRESUMEN
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.