Cyanobacteria are the earliest known oxygenic photosynthetic organisms on Earth, and they played decisive roles in the evolution of the environment and the life on our planet. Cell morphology and cell size of different cyanobacteria species vary widely, but each species has an inheritable and distinct cell morphology and cell size that is stably maintained through the generations. The underlying mechanisms of such a homeostasis have been unknown.    

The research group led by Professor ZHANG Cheng-Cai from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences reported in PNAS a new cell size regulation mechanism that represents an important advance in understanding cell morphology and cell size controlling of cyanobacteria .  

Previous studies by Prof. Zhang's team have found that the second messenger c-di-GMP may be an intracellular proxy for cell size control in the filamentous cyanobacterium Anabaena PCC 7120. However, it was unclear how this chemical signal is perceived in cells. In addition, all c-di-GMP receptors known in other organisms are not conserved in cyanobacteria, posing a challenge to understand the physiological function of c-di-GMP in cyanobacteria.    

In this study, the researchers identified and characterized the first c-di-GMP receptor, CdgR, from the cyanobacterium Anabaena. According to crystal structural analysis and genetic studies, CdgR binds c-di-GMP at the dimer interface, and this binding is required for the control of cell size in a c-di-GMP-dependent manner.    

Combined biochemistry analysis and genetic analysis, the researchers also discovered that CdgR functions by interacting with a global transcription factor DevH, and that this interaction was inhibited by c-di-GMP.   

“This study provides a novel mechanism of cell size regulation. Some mutants associated with genes of this pathway produce a lethal phenotype, indicating that this signaling pathway paly critical functions in this cyanobacterium. Cyanobacteria has enormous promise in biofuel production, CO2 mitigation, and other applications. The exploration of the cell size and cell morphology control is critical for customizing and constructing cyanobacterial cells with particular features adapted to biotechnological applications using synthetic biology approach,” Prof. Zhang said.   

CdgR is highly conserved in cyanobacteria. Therefore, this study lays the groundwork for the understanding of the roles of c-di-GMP signaling in these organisms, including important physiological processes such as photoregulation, biofilm formation, cell motility, and cyanobacteria bloom formation.   

Professor Zhang 's team has been devoted to basic research on prokaryotic cell morphogenesis and synthetic biology research related to the cyanobacterial bloom control. This work is another important achievement of the team after their publications earlier in PNAS and PNAS Nexus about the coordination mechanism of cell division and development.  

 
Studying cell morphology/size can lay the foundation for customizing and constructing cyanobacteria cells with application prospects through synthetic biology. (Image by IHB)  

(Editor: MA Yun)