title: A RelA-dependent two-tiered regulated proteolysis cascade controls synthesis of a contact-dependent intercellular signal in Myxococcus xanthus.
abstract: Proteolytic cleavage of precursor proteins to generate intercellular signals is a common mechanism in all cells. In Myxococcus xanthus the contact-dependent intercellular C-signal is a 17 kDa protein (p17) generated by proteolytic cleavage of the 25 kDa csgA protein (p25), and is essential for starvation-induced fruiting body formation. p25 accumulates in the outer membrane and PopC, the protease that cleaves p25, in the cytoplasm of vegetative cells. PopC is secreted in response to starvation, therefore, restricting p25 cleavage to starving cells. We focused on identifying proteins critical for PopC secretion in response to starvation. PopC secretion depends on the (p)ppGpp synthase RelA and the stringent response, and is regulated post-translationally. PopD, which is encoded in an operon with PopC, forms a soluble complex with PopC and inhibits PopC secretion whereas the integral membrane AAA+ protease FtsH(D) is required for PopC secretion. Biochemical and genetic evidence suggest that in response to starvation, RelA is activated and induces the degradation of PopD thereby releasing pre-formed PopC for secretion and that FtsH(D) is important for PopD degradation. Hence, regulated PopC secretion depends on regulated proteolysis. Accordingly, p17 synthesis depends on a proteolytic cascade including FtsH(D) -dependent degradation of PopD and PopC-dependent cleavage of p25.
authors.affiliation: Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch Str. 10, 35043 Marburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Konovalova
authors.forename: Stephanie
authors.initials: S
authors.lastname: Löbach
authors.forename: Lotte
authors.initials: L
authors.lastname: Søgaard-Andersen
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008025:Ligases / Q000378:metabolism*; D016941:Myxococcus xanthus / Q000378:metabolism / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D001426:Bacterial Proteins; C063576:CsgA protein, Myxococcus xanthus; D036341:Intercellular Signaling Peptides and Proteins; D010447:Peptide Hydrolases; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases