info:eu-repo/semantics/article
Utilization of extracellular information before ligand-receptor binding reaches equilibrium expands and shifts the input dynamic range
Fecha
2014-08Registro en:
Ventura, Alejandra; Bush, Alan; Vasen, Gustavo; Goldin, Matías Alejandro; Burkinshaw, Brianne; et al.; Utilization of extracellular information before ligand-receptor binding reaches equilibrium expands and shifts the input dynamic range; National Academy Of Sciences; Proceedings Of The National Academy Of Sciences Of The United States Of America; 111; 37; 8-2014; 3860-3869
0027-8424
CONICET Digital
CONICET
Autor
Ventura, Alejandra
Bush, Alan
Vasen, Gustavo
Goldin, Matías Alejandro
Burkinshaw, Brianne
Bhattacharjee, Nirveek
Folch, Albert
Brent, Roger
Chernomoretz, Ariel
Colman Lerner, Alejandro Ariel
Resumen
Cell signaling systems sense and respond to ligands that bind cell surface receptors. These systems often respond to changes in the concentration of extracellular ligand more rapidly than the ligand equilibrates with its receptor. We demonstrate, by modeling and experiment, a general “systems level” mechanism cells use to take advantage of the information present in the early signal, before receptor binding reaches a new steady state. This mechanism, preequilibrium sensing and signaling (PRESS), operates in signaling systems in which the kinetics of ligand-receptor binding are slower than the downstream signaling steps, and it typically involves transient activation of a downstream step. In the systems where it operates, PRESS expands and shifts the input dynamic range, allowing cells to make different responses to ligand concentrations so high as to be otherwise indistinguishable. Specifically, we show that PRESS applies to the yeast directional polarization in response to pheromone gradients. Consideration of preexisting kinetic data for ligand-receptor interactions suggests that PRESS operates in many cell signaling systems throughout biology. The same mechanism may also operate at other levels in signaling systems in which a slow activation step couples to a faster downstream step.