Source: Lipshtat A, Jayaraman G, He JC, Iyengar R. Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1247-52. Epub 2009 Dec 28.
Abstract
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.
PMID: 20080566 | PMCID: PMC2824311 | EndNote Citation
Supplemental Files: PNAS_switch.m, PNAS_switch.vcml, PNAS_switch.pdf