Major Tom to Ground Control: How Lipoproteins Communicate Extracytoplasmic Stress to the Decision Center of the Cell.

The envelope of bacteria is a complex multilayered shield that ensures multiple essential functions, including protecting the cell from external assaults. Hence, bacterial cells have evolved intricate mechanisms called envelope stress response systems (ESRS) to monitor all kinds of perturbations affecting the integrity of their envelope and to mount an appropriate response to contain or repair the damage. In the model bacterium Escherichia coli, several ESRS are built around a two-component system, in which envelope stress triggers a phosphotransfer between a sensor protein in the inner membrane of the envelope and a response regulator in the cytoplasm. In this review, we focus on two major ESRS in E. coli, the Rcs and Cpx pathways, in which additional proteins not directly involved in the phosphotransfer modulate signal transduction. Both the Rcs and Cpx systems can be turned on by a lipoprotein anchored in the outer membrane, RcsF and NlpE, respectively, providing a molecular connection between the most exterior layer of the envelope and the ground control center in the cytoplasm. Here, we review how these two lipoproteins, which share a striking set of features while being distinct in several aspects, act as sentinels at the front line of the bacterium by sensing and transducing stress to the downstream components of the Rcs and Cpx systems.