POSTERS - BLAST X - University of Utah
POSTERS - BLAST X - University of Utah
POSTERS - BLAST X - University of Utah
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<strong>BLAST</strong> X Poster #16<br />
MODELING SCAFFOLD PHOSPHORYLATION AS AN ADAPTATION MECHANISM IN<br />
BACTERIAL CHEMOTAXIS<br />
Roger Alexander, Adam Bildersee, and Thierry Emonet<br />
Department <strong>of</strong> Molecular, Cellular, and Developmental Biology, Kline Biology Tower 1054, Yale<br />
<strong>University</strong>, New Haven, CT 06520<br />
Bacterial chemotaxis is one <strong>of</strong> the best-understood signaling networks in biology.<br />
Chemotaxis in E. coli is a model system for thoroughly understanding a behavioral phenotype at<br />
the molecular level. Chemotaxis has been studied experimentally in a variety <strong>of</strong> other species,<br />
and modeled in B. subtilis, but no dynamical models <strong>of</strong> chemotaxis network architectures from<br />
other species have yet been built. A key feature <strong>of</strong> the chemotaxis signal transduction network<br />
is adaptation: after a transient response to a step change in input stimulus, its activity returns to<br />
its pre-stimulus steady state level, allowing the system to respond to higher stimulus<br />
concentrations without saturation. In E. coli, adaptation is mediated through two enzymes, CheR<br />
and CheB, that methylate and demethylate the sensory receptors. In this work we consider<br />
scaffold phosphorylation as an adaptation mechanism complementary to receptor methylation.<br />
The receptors form a sensory array in the membrane at the cell pole; the scaffold protein<br />
couples the receptors to the kinase CheA which they activate. In all current dynamical models <strong>of</strong><br />
chemotaxis, the receptors, scaffolds, and kinases are treated as a single species, a receptorkinase<br />
complex. This is understandable, because in E. coli, the scaffold CheW is a passive<br />
mediator <strong>of</strong> the receptor-kinase interaction. However, in other organisms, the scaffold CheV<br />
has not only a CheW scaffold domain, but also a receiver domain that is the target <strong>of</strong><br />
phosphorylation by the kinase. Bacillus subtilis has both CheW and CheV scaffolds, and<br />
phosphorylation <strong>of</strong> CheV is known to be necessary for adaptation. In B. subtilis, phospho-CheV<br />
decouples receptor from kinase, so it actively mediates their interaction. The evolutionary<br />
distance between B. subtilis and E. coli is wide, and there are other differences between their<br />
chemotaxis network architectures that confound an understanding <strong>of</strong> the specific role <strong>of</strong> scaffold<br />
phosphorylation. Therefore we choose to focus on a close relative <strong>of</strong> E. coli, Salmonella<br />
enterica serovar typhimurium. The chemotaxis network architecture in Salmonella is almost<br />
identical to that in E. coli, except that Salmonella has both CheW and CheV scaffolds. A mutant<br />
Salmonella that lacks methylation-based adaptation is able to adapt partially, presumably<br />
through its scaffold phosphorylation mechanism. We have built a dynamical model <strong>of</strong> the<br />
chemotaxis network in E. coli that explicitly represents receptor-kinase coupling by the scaffold.<br />
We have extended that model to include scaffold phosphorylation in Salmonella. Our model <strong>of</strong> a<br />
Salmonella mutant that lacks methylation exhibits partial adaptation, consistent with<br />
experimental results. This work is the first step in a long-range program to explore how<br />
evolutionary changes in chemotaxis network architecture affects the dynamics and function <strong>of</strong><br />
the network. Evolution <strong>of</strong> dynamic signal transduction networks is an important emerging<br />
research area in systems biology.<br />
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