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Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues.


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.

SUBMITTER: Lipshtat A 

PROVIDER: S-EPMC2824311 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues.

Lipshtat Azi A   Jayaraman Gomathi G   He John Cijiang JC   Iyengar Ravi R  

Proceedings of the National Academy of Sciences of the United States of America 20091228 3


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  ...[more]

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