Load-induced modulation of signal transduction networks

• Autores: Jiang, Peng; Ventura, Alejandra; Sontag, Eduardo D.; Merajver, Sofia D.; Ninfa, Alexander J.; Del Vecchio, Domitilla
• Año de publicación: 2011
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: BIOCHEMISTRY AND MOLECULAR BIOLOGY; CELL BIOLOGY; CASCADES; INSULATION
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Biological signal transduction networks are commonly viewed as circuits that pass along information—in the process amplifying signals, enhancing sensitivity, or performing other signal-processing tasks—to transcriptional and other components. Here, we report on a “reverse-causality” phenomenon, which we call load-induced modulation. Through a combination of analytical and experimental tools, we discovered that signaling was modulated, in a surprising way, by downstream targets that receive the signal and, in doing so, apply what in physics is called a load. Specifically, we found that non-intuitive changes in response dynamics occurred for a covalent modification cycle when load was present. Loading altered the response time of a system, depending on whether the activity of one of the enzymes was maximal and the other was operating at its minimal rate or whether both enzymes were operating at submaximal rates. These two conditions, which we call “limit regime” and “intermediate regime,” were associated with increased or decreased response times, respectively. The bandwidth, the range of frequency in which the system can process information, decreased in the presence of load, suggesting that downstream targets participate in establishing a balance between noise-filtering capabilities and a circuit’s ability to process high-frequency stimulation. Nodes in a signaling network are not independent relay devices, but rather are modulated by their downstream targets.
Fil: Jiang, Peng. University of Michigan; Estados Unidos
Fil: Ventura, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular. Laboratorio de Fisiología y Biología Molecular; Argentina
Fil: Sontag, Eduardo D.. Rutgers University; Estados Unidos
Fil: Merajver, Sofia D.. University of Michigan; Estados Unidos
Fil: Ninfa, Alexander J.. University of Michigan; Estados Unidos
Fil: Del Vecchio, Domitilla. Massachusetts Institute of Technology; Estados Unidos