%A Lipshtat, Azi
%A Jayaraman, Gomathi
%A He, John Cijiang
%A Iyengar, Ravi
%T Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues
%0 Journal Article
%D 2010
%8 January 19, 2010
%J Proceedings of the National Academy of Sciences
%P 1247-1252
%R 10.1073/pnas.0908647107
%V 107
%N 3
%U http://www.pnas.org/content/107/3/1247.abstract
%X Cells often mount ultrasensitive (switch-like) responses to stimuli. The design principles underlying many switches are not known. We computationally studied the switching behavior of GTPases, and found that this first-order kinetic system can show ultrasensitivity. Analytical solutions indicate that ultrasensitive first-order reactions can yield switches that respond to signal amplitude or duration. The three-component GTPase system is analogous to the physical fermion gas. This analogy allows for an analytical understanding of the functional capabilities of first-order ultrasensitive systems. Experiments show amplitude- and time-dependent Rap GTPase switching in response to Cannabinoid-1 receptor signal. This first-order switch arises from relative reaction rates and the concentrations ratios of the activator and deactivator of Rap. First-order ultrasensitivity is applicable to many systems where threshold for transition between states is dependent on the duration, amplitude, or location of a distal signal. We conclude that the emergence of ultrasensitivity from coupled first-order reactions provides a versatile mechanism for the design of biochemical switches.