Roles of methylation and phosphorylation in the bacterial sensing system.

Chemotaxis is an intriguing model system for the study of second-messenger pathways. One of the puzzles of second-messenger pathways in eukaryotic cells has been that many of these pathways interact, with one pathway either desensitizing or sensitizing an alternate messenger pathway. The chemotaxis system offered a particularly interesting chance to analyze such systems, because one of them is a methylation pathway and the other a phosphorylation pathway. The above description indicates that these two pathways interact with each other in a highly sophisticated way to produce an extremely important survival system. The stimulus on a receptor activates an excitation system that operates through phosphorylation, or the inhibition of phosphorylation, depending on whether the stimulus is a repellent or an attractant. That system ultimately generates or inhibits phosphorylation of a small peptide, the CheY protein, which apparently is the response regulator. The instant that this fast excitation is generated by a change in gradient, the change in conformation of the protein sets in motion a second process, i.e., the adaptation. That is a device which, over a longer period of time, has two functions: It serves as the comparator, which allows the comparison of the past with the present, essential for deletion of a gradient; it also sets in motion the reset to zero, so that the bacterium will not be overwhelmed by any one stimulus but can use all of its receptors to optimize its environment. These two systems by themselves are adequate for chemotaxis, but there is a further elegent complexity: The excitation system feeds back into the adaptation system to produce an asymmetry in the responses. The reason for that asymmetry is that the bacterium wishes to travel in the wrong direction only long enough to produce a detectable signal that it is migrating incorrectly. It wishes to keep swimming in the positive direction as long as the signals indicate that the direction is favorable. Hence, the feedback between the phosphorylation and methylation system involves further fine tuning.