Dual Regulation with Ser/Thr Kinase Cascade and a His/Asp TCS in Myxococcus xanthus

Abstract

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.

Eukaryote-Like Serine/Threonine Kinases and Phosphatases in Bacteria

“…If unfavorable conditions persist, the aggregated cells can form metabolically dormant myxospores until nutrients become available again. The tight regulation of this complex developmental cycle has been reviewed in detail (69). Briefly, FruA is a key transcription factor that regulates the expression of a large number of genes involved in both fruiting body formation and sporulation.…”

“…The eSTK Pkn14 also regulates MrpC by phosphorylating it on a Thr residue(s), reducing its affinity for both its own promoter and the fruA promoter (119,120). The transmembrane eSTK Pkn8 phosphorylates Pkn14, and it has been suggested that Pkn8 and -14 form an eSTK cascade that inhibits the activity of MrpC during vegetative growth (69,119) (Fig. 5).…”

The Eukaryote-Like Serine/Threonine Kinase STK Regulates the Growth and Metabolism of Zoonotic Streptococcus suis

“…The eSTKs have been widely studied for their roles in diverse biological processes, including development (Zhang, 1993; Nádvorník et al, 1999; Inouye and Nariya, 2008), cell competence (Hussain et al, 2006), cell division, and cell wall synthesis (Deol et al, 2005; Fernandez et al, 2006; Ruggiero et al, 2012), central and secondary metabolism (Lee et al, 2002; Sawai et al, 2004), biofilm formation (Hussain et al, 2006; Liu et al, 2011), stress response (Neu et al, 2002; Mata-Cabana et al, 2012), and virulence (Madec et al, 2002; Rajagopal et al, 2003; Echenique et al, 2004). Gene expression profiles have proven their global regulatory roles in cellular processes (Sasková et al, 2007; Donat et al, 2009).…”

Two-Component Signal Transduction Systems That Regulate the Temporal and Spatial Expression of Myxococcus xanthus Sporulation Genes

“…For a discussion of FruA's roles in aggregation and in the C-signaling network, see previous reviews in references 24,88,89, and 32; they will not be discussed in detail here. The results of several studies indicate that FruA plays a direct role in the regulation of sporulation.…”