| Title: | Utilization of extracellular information before ligand-receptor binding reaches equilibrium expands and shifts the input dynamic range |
| Author(s): | Ventura AC; Bush A; Vasen G; Goldin MA; Burkinshaw B; Bhattacharjee N; Folch A; Brent R; Chernomoretz A; Colman-Lerner A; |
| Address: | "Institute of Physiology, Molecular Biology, and Neuroscience (IFIBYNE), University of Buenos Aires (UBA)-National Scientific and Technical Research Council (CONICET), Department of Physiology, Molecular, and Cell Biology, School of Exact and Natural Sciences (FCEN). Department of Bioengineering, University of Washington, Seattle, WA 98195; and. Fundacion Instituto Leloir, C1405BWE Buenos Aires, Argentina; Physics Institute of Buenos Aires (IFIBA), CONICET, and Department of Physics, FCEN, UBA, C1428EGA Buenos Aires, Argentina; Fundacion Instituto Leloir, C1405BWE Buenos Aires, Argentina; Institute of Physiology, Molecular Biology, and Neuroscience (IFIBYNE), University of Buenos Aires (UBA)-National Scientific and Technical Research Council (CONICET), Department of Physiology, Molecular, and Cell Biology, School of Exact and Natural Sciences (FCEN), colman-lerner@fbmc.fcen.uba.ar" |
| ISSN/ISBN: | 1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking) |
| Abstract: | "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, pre-equilibrium 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" |
| Keywords: | "Cell Polarity Extracellular Space/*metabolism Kinetics Ligands Models, Biological Protein Binding Receptors, Cell Surface/*metabolism Saccharomyces cerevisiae/*cytology/*metabolism *Signal Transduction Time Factors binding kinetics cellular signaling dose;Neuroscience;" |
| Notes: | "MedlineVentura, Alejandra C Bush, Alan Vasen, Gustavo Goldin, Matias A Burkinshaw, Brianne Bhattacharjee, Nirveek Folch, Albert Brent, Roger Chernomoretz, Ariel Colman-Lerner, Alejandro eng R01 GM097479/GM/NIGMS NIH HHS/ 1R01GM097479-01/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2014/08/31 Proc Natl Acad Sci U S A. 2014 Sep 16; 111(37):E3860-9. doi: 10.1073/pnas.1322761111. Epub 2014 Aug 29" |
