Regulation of the general stress response sigma factor ^T by Lon-mediated proteolysis

The Lon protease is widely conserved in both prokaryotic and eukaryotic organisms and fulfills important regulatory functions. Nevertheless, the number of identified Lon substrates is limited in most organisms, and the precise role of Lon in regulating these proteins is poorly understood. Here, we describe the alpha-proteobacterial general stress response sigma factor sigma(T) as a novel Lon substrate in Caulobacter crescentus. Based on previously published quantitative proteomics data, we find sigma(T) to be a promising putative Lon substrate and confirm a direct role of Lon in degrading sigma T. We show that Lon contributes to the downregulation of sigma(T )abundance under optimal conditions and during recovery from sucrose-induced osmotic stress. Furthermore, the presence of the Lon activity regulator LarA enhances Lon-mediated degradation of sigma(T) in vitro and reduces sigma(T) levels in vivo indicating a role of LarA in modulating Lon-mediated degradation of sigma(T). Together, our results highlight the importance of Lon during the recovery phase following stress exposure by adjusting the concentrations of critical regulators of stress responses.