Energy drives the dynamic localization of cyanobacterial nitrogen regulators during diurnal cycles

Espinosa, José; Labella, José Ignacio Vega; Cantos, Raquel; Contreras, Asunción

doi:10.1111/1462-2920.14071

Cited by 19 publications

(24 citation statements)

References 56 publications

(82 reference statements)

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“…The gene encoding P II could not be deleted in S. elongatus unless the pipX gene was previously inactivated (Espinosa et al, 2009 ). Further studies led to the conclusion that decreasing the P II /PipX ratio results in lethality in S. elongatus , indicating that PipX sequestration into P II -PipX complexes is crucial for survival and implicating both proteins in the regulation of essential processes (Espinosa et al, 2010 , 2018 ; Laichoubi et al, 2012 ). The ability of P II to prevent the toxicity of PipX suggests that P II acts as a PipX sink even under conditions in which the affinity for NtcA would be highest, supporting the idea that not all PipX effects are related to its role as NtcA co-activator.…”

Section: The Pipx Regulatory Network In Quantitative Perspectivementioning

confidence: 99%

The PII-NAGK-PipX-NtcA Regulatory Axis of Cyanobacteria: A Tale of Changing Partners, Allosteric Effectors and Non-covalent Interactions

Forcada-Nadal

Llácer

Contreras

et al. 2018

Front. Mol. Biosci.

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PII, a homotrimeric very ancient and highly widespread (bacteria, archaea, plants) key sensor-transducer protein, conveys signals of abundance or poorness of carbon, energy and usable nitrogen, converting these signals into changes in the activities of channels, enzymes, or of gene expression. PII sensing is mediated by the PII allosteric effectors ATP, ADP (and, in some organisms, AMP), 2-oxoglutarate (2OG; it reflects carbon abundance and nitrogen scarcity) and, in many plants, L-glutamine. Cyanobacteria have been crucial for clarification of the structural bases of PII function and regulation. They are the subject of this review because the information gathered on them provides an overall structure-based view of a PII regulatory network. Studies on these organisms yielded a first structure of a PII complex with an enzyme, (N-acetyl-Lglutamate kinase, NAGK), deciphering how PII can cause enzyme activation, and how it promotes nitrogen stockpiling as arginine in cyanobacteria and plants. They have also revealed the first clear-cut mechanism by which PII can control gene expression. A small adaptor protein, PipX, is sequestered by PII when nitrogen is abundant and is released when is scarce, swapping partner by binding to the 2OG-activated transcriptional regulator NtcA, co-activating it. The structures of PII-NAGK, PII-PipX, PipX alone, of NtcA in inactive and 2OG-activated forms and as NtcA-2OG-PipX complex, explain structurally PII regulatory functions and reveal the changing shapes and interactions of the T-loops of PII depending on the partner and on the allosteric effectors bound to PII. Cyanobacterial studies have also revealed that in the PII-PipX complex PipX binds an additional transcriptional factor, PlmA, thus possibly expanding PipX roles beyond NtcA-dependency. Further exploration of these roles has revealed a functional interaction of PipX with PipY, a pyridoxal-phosphate (PLP) protein involved in PLP homeostasis whose mutations in the human ortholog cause epilepsy. Knowledge of cellular levels of the different components of this PII-PipX regulatory network and of KD values for some of the complexes provides the basic background for gross modeling of the system at high and low nitrogen abundance. The cyanobacterial network can guide searches for analogous components in other organisms, particularly of PipX functional analogs.

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Section: The Pipx Regulatory Network In Quantitative Perspectivementioning

confidence: 99%

The PII-NAGK-PipX-NtcA Regulatory Axis of Cyanobacteria: A Tale of Changing Partners, Allosteric Effectors and Non-covalent Interactions

Forcada-Nadal

Llácer

Contreras

et al. 2018

Front. Mol. Biosci.

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“…Furthermore, 2-OG directly binds to the global nitrogen control factor, NtcA, thereby tuning its activity. Binding of PipX by NtcA is antagonized by the P II signal transduction protein, which preferentially binds PipX at elevated ADP levels (Zeth et al, 2014;Lüddecke and Forchhammer, 2015;Espinosa et al, 2018). This enables NtcA to activate genes for the acquisition of alternate nitrogen sources and for increased GS activity (Luque and Forchhammer, 2008;Giner-Lamia et al, 2017).…”

Section: Metabolic Responses To Nitrogen Starvationmentioning

confidence: 99%

“…This enables NtcA to activate genes for the acquisition of alternate nitrogen sources and for increased GS activity (Luque and Forchhammer, 2008;Giner-Lamia et al, 2017). Binding of PipX by NtcA is antagonized by the P II signal transduction protein, which preferentially binds PipX at elevated ADP levels (Zeth et al, 2014;Lüddecke and Forchhammer, 2015;Espinosa et al, 2018). These responses link nitrogen sensing with the detection of cellular energy level.…”

Section: Metabolic Responses To Nitrogen Starvationmentioning

confidence: 99%

Nitrogen chlorosis in unicellular cyanobacteria – a developmental program for surviving nitrogen deprivation

Forchhammer

Schwarz

2018

Environmental Microbiology

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Summary Cyanobacteria evolved sophisticated mechanisms allowing them to cope with environmental depletion of combined nitrogen. Here, we describe progress in understanding the processes involved in acclimation of nondiazotrophic cyanobacteria to nitrogen shortage, known as nitrogen chlorosis. The process includes immediate metabolic changes and degradation of light harvesting complexes as well as long‐term acclimation responses. Consequently, quiescent cells substantially differing from vegetative cells are obtained. Thus, the process leading to these considerable metabolic and morphological changes is referred to as a developmental program. Current understanding of the relevant regulatory processes depicts an intricate mechanism involving modulation of transcription activators by proteinaceous interacting components, as well as by small metabolites reporting the energy status and carbon–nitrogen balance of the cell. In addition, we describe in detail the quiescent state characterizing cells under prolonged starvation and the process of recovery from this dormant chlorotic state. Accumulated data provide an in depth understanding of the mechanisms accompanying the cycling of cyanobacterial cells between vegetative growth, the quiescent‐state and the recovery program, allowing them to regain proliferative growth upon nutrient replenishment.

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“…On the other hand, addition of IPTG resulted in toxicity to cells (Supporting Information Fig. S2), a result reflecting the toxicity of PipX when the PipX/PII ratio is increased above a certain threshold (Espinosa et al, 2009;Laichoubi et al, 2012;Espinosa et al, 2018).…”

Section: Pipx Acts In Cis To Increase Pipy Levelsmentioning

confidence: 99%

“…PII and PipX mediate protein-protein interactions with regulatory targets that include transcriptional regulators, enzymes and transporters involved in nitrogen and/or carbon assimilation. They both display distinct localization patterns during diurnal cycles, co-localizing at dark periods in an energy dependent manner (Espinosa et al, 2018). PII perceives metabolic information by competitive binding of ATP or ADP and by synergistic binding of ATP and 2-oxoglutarate (2-OG).…”

Section: Introductionmentioning

confidence: 99%

The nitrogen regulator PipX acts in cis to prevent operon polarity

Cantos

Labella

Espinosa

et al. 2018

Environ Microbiol Rep

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Cyanobacteria, phototrophic organisms performing oxygenic photosynthesis, must adapt their metabolic processes to important environmental challenges, like those imposed by the succession of days and nights. Not surprisingly, certain regulatory proteins are found exclusively in this phylum. One of these unique factors, PipX, provides a mechanistic link between signals of carbon/nitrogen and of energy, transduced by the signalling protein PII, and the control of gene expression by the global nitrogen regulator NtcA. Here we report a new regulatory function of PipX: enhancement in cis of pipY expression, a gene encoding a universally conserved protein involved in amino/keto acid and Pyridoxal phosphate homeostasis. In Synechococcus elongatus and many other cyanobacteria these genes are expressed as a bicistronic pipXY operon. Despite being cis-acting, polarity suppression by PipX is nevertheless reminiscent of the function of NusG paralogues typified by RfaH, which are non-essential operon-specific bacterial factors acting in trans to upregulate horizontally-acquired genes. Furthermore, PipX and members of the NusG superfamily share a TLD/KOW structural domain, suggesting regulatory interactions of PipX with the translation machinery. Our results also suggest that the cis-acting function of PipX is a sophisticated regulatory strategy for maintaining appropriate PipX-PipY stoichiometry.

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Energy drives the dynamic localization of cyanobacterial nitrogen regulators during diurnal cycles

Cited by 19 publications

References 56 publications

The PII-NAGK-PipX-NtcA Regulatory Axis of Cyanobacteria: A Tale of Changing Partners, Allosteric Effectors and Non-covalent Interactions

The PII-NAGK-PipX-NtcA Regulatory Axis of Cyanobacteria: A Tale of Changing Partners, Allosteric Effectors and Non-covalent Interactions

Nitrogen chlorosis in unicellular cyanobacteria – a developmental program for surviving nitrogen deprivation

The nitrogen regulator PipX acts in cis to prevent operon polarity

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