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The Sixty-Four-Thousand-Dollar Question: How Signals are Transmitted Across Cell Membrane

Bacteria can occur almost anywhere on earth and exist under the most varying conditions. If these tiny, microscopic organisms are to survive in these environments, they need to be able to rapidly detect changes in their surroundings and react to them. Scientists at the Johannes Gutenberg University of Mainz are currently investigating how bacteria manage to pass information on their environment across their membranes into their cell nuclei. "The sixty-four-thousand- dollar question is how signals are transmitted across the cell membrane," explains Professor Gottfried Unden of the Institute of Microbiology and Vinology. Working in collaboration with the Max Planck Institute for Biophysical Chemistry in Göttingen, his research group has demonstrated that structural alterations to membrane-based sensors play a major role in the transfer of signals.

Some bacteria possess more than 100 different sensors that they use to form a picture of their environment. These sensors can show, for example, whether nutrient substrates and/or oxygen are present in the immediate neighborhood of the cell and what the external status of temperature and light is like. These sensors are mainly located in the cell membrane, i.e., the layer separating bacteria cells from the environment. From there they then transmit signals into the cell nucleus. Thanks to the development of new methods of isolating these sensors and of other innovative techniques, it is now possible to discover how all this works. The researchers in Mainz have also managed to modify a sensor that detects an important bacterial substrate so that it can be analyzed making use of new spectroscopic techniques. "This is the first time that solid-body nuclear magnetic resonance (NMR) spectroscopy has been used to investigate large membrane proteins," stated Professor Unden. In addition to this functional analysis, the structural analysis undertaken by the biophysicist team in Göttingen headed by Professor Marc Baldus has identified important details of the signal transmission process: a stimulus molecule – carbonic acid in this case – binds to a part of the sensor that protrudes from the cell. This appears to result in dissolution of the ordered structure of that segment of the sensor within the cell that is in non-stimulated status. It seems that it is this plasticity that elicits the subsequent activation of the enzymatic reaction cascade within the cell. This results in the cellular response, which, for example, can take the form of neosynthesis of enzymes or the development of protective mechanisms.

In addition to the new findings on signal transmission published in Nature Structural and Molecular Biology, the microbiologists of Mainz University have discovered a previously unknown and exceptional method of signal detection employed by the same sensor (designated DcuS), which they discuss in an article in the Journal of Biological Chemistry. This shows that bacteria react not only to their extracellular environment, but also to the intracellular situation. It is becoming apparent that it is not the sensors alone that detect stimuli. A second stimulus detection pathway is represented by the transport system that channels substrates into the cell. Once the substrate – carbonic acid – has been taken up, the transporter notifies the sensor of this. Prof. Unden added, "We have been able to identify that segment of the transporter that is responsible for the control of sensor functioning. The transporter is of fundamental importance for the function of the sensor. Without the transporter, the sensor does not work correctly and is constantly in activated status," explained Professor Unden, who suspects that this function-related feedback on metabolic and transport activity is often more important for a cell than information concerning concentrations only.

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