Dual regulation with Ser/Thr kinase cascade and a His/Asp TCS in Myxococcus xanthus

Fruiting body development of Myxococcus xanthus is propelled by temporal gene expression directed via stage-specific intercellular signaling pathways. M. xanthus exhibits social behaviors during its complex life cycle and is a potential source for production of natural products such as secondary metabolites. The numerous signaling pathways of M. xanthus consist of not only the two-component His-Asp phosphorelay system (TCS) but also protein Ser/Thr kinases (PSTKs) that regulate gene expression, motility and multicellular development. Recent studies have uncovered the unique molecular regulatory mechanism of MrpC, a transcription factor essential for fruiting body development and sporulation. mrpC expression is activated early in development by MrpB, which belongs to the NtrC family of TCS. MrpC, is, in turn, a transcriptional activator of fruA that encodes another key transcription factor, FruA. FruA is essential for fruiting body development and sporulation and regulates positively and negatively the synthesis of many developmental proteins. In addition, expression of mrpC during vegetative growth is kept at a low level by the PSTK Pkn8-Pkn14 kinase cascade which negatively regulates MrpC-binding activity to its own promoter. Therefore, M. xanthus utilizes a novel dual system with both eukaryotic PSTK cascade and prokaryotic TCS signaling systems to tightly and precisely regulate MrpC levels, which activate timely fruA expression and propel fruiting body development and sporulation.