Carbon/nitrogen (C/N) balance sensing is a key requirement for the maintenance of cellular homeostasis. Therefore, cyanobacteria have evolved a sophisticated signal transduction network targeting the metabolite 2-oxoglutarate (2-OG), the carbon skeleton for nitrogen assimilation. It serves as a status reporter for the cellular C/N balance that is sensed by transcription factors NtcA and NdhR and the versatile PII-signaling protein. The PII protein acts as a multitasking signal-integrating regulator, combining the 2-OG signal with the energy state of the cell through adenyl-nucleotide binding. Depending on these integrated signals, PII orchestrates metabolic activities in response to environmental changes through binding to various targets. In addition to 2-OG, other status reporter metabolites have recently been discovered, mainly indicating the carbon status of the cells. One of them is cAMP, which is sensed by the PII-like protein SbtB. The present review focuses, with a main emphasis on unicellular model strains Synechoccus elongatus and Synechocystis sp. PCC 6803, on the physiological framework of these complex regulatory loops, the tight linkage to metabolism and the molecular mechanisms governing the signaling processes.

PII proteins are multitasking information-processing proteins occurring in bacteria, archaea, and plastids, decoding the metabolic state of the cells and providing this information to various regulatory targets. Research in recent years identified a wide range of novel PII targets mainly through ligand fishing assays, indicating that PII proteins evolved into major regulatory hubs of cellular metabolism. PII proteins orchestrate not only key steps of nitrogen and carbon metabolism but rather control a wide range of transporters and can also regulate the production of signaling molecules (c-di-GMP) and cofactors (NAD⁺). A recently identified class of PII-interacting proteins, which by themselves have no enzymatic activity, modulate cellular processes through protein interactions, further extending the regulatory range of PII proteins.

Significance: Life on Earth depends on photosynthetic CO ₂ fixation to form organic carbon. This process evolved in cyanobacteria and was later conveyed to eukaryotes, giving rise to plastids in algae and plants. To cope with low atmospheric CO ₂ concentrations that developed over the course of evolution, cyanobacteria evolved a CO ₂ -concentrating mechanism (CCM), which elevates CO ₂ levels in the vicinity of RubisCO, the key enzyme of CO ₂ fixation. Here we describe a conserved cyclic AMP receptor protein, SbtB, which participates in the sensing of fluctuating C _i levels to regulate the cyanobacterial CCM system. SbtB represents a new principle of C _i sensing, which is important for acclimation to varying C _i regimes in the ecological niches of cyanobacteria.

Summary: The PII superfamily consists of signal transduction proteins found in all domains of life. Canonical PII proteins sense the cellular energy state through the competitive binding of ATP and ADP, and carbon/nitrogen balance through 2‐oxoglutarate binding. The ancestor of Archaeplastida inherited its PII signal transduction protein from an ancestral cyanobacterial endosymbiont. Over the course of evolution, plant PII proteins acquired a glutamine‐sensing C‐terminal extension, subsequently present in all Chloroplastida PII proteins. The PII proteins of various algal strains (red, green and nonphotosynthetic algae) have been systematically investigated with respect to their sensory and regulatory properties. Comparisons of the PII proteins from different phyla of oxygenic phototrophs (cyanobacteria, red algae, Chlorophyta and higher plants) have yielded insights into their evolutionary conservation vs adaptive properties. The highly conserved role of the controlling enzyme of arginine biosynthesis, N‐acetyl‐l‐glutamate kinase (NAGK), as a main PII‐interactor has been demonstrated across oxygenic phototrophs of cyanobacteria and Archaeplastida. In addition, the PII signalling system of red algae has been identified as an evolutionary intermediate between that of Cyanobacteria and Chloroplastida. In this review, we consider recent advances in understanding metabolic signalling by PII proteins of the plant kingdom.