scholarly journals The Multiple Regulatory Relationship Between RNA-Chaperone Hfq and the Second Messenger c-di-GMP

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Fu ◽  
Zhaoqing Yu ◽  
Li Zhu ◽  
Zhou Li ◽  
Wen Yin ◽  
...  
Keyword(s):  
Second Messenger ◽  
Regulatory Relationship ◽  
Rna Chaperone ◽  
Chaperone Protein ◽  
Regulatory Systems ◽  
Metabolic Systems ◽  
Two Factors ◽  
Solid Foundation ◽  
Second Messenger Signaling ◽  
Post Transcriptional Regulation

RNA chaperone protein Hfq is an important post-transcriptional regulator in bacteria, while c-di-GMP is a second messenger signaling molecule widely distributed in bacteria. Both factors have been found to play key roles in post-transcriptional regulation and signal transduction pathways, respectively. Intriguingly, the two factors show some common aspects in the regulation of certain physiological functions such as bacterial motility, biofilm formation, pathogenicity and so on. Therefore, there may be regulatory relationship between Hfq and c-di-GMP. For example, Hfq can directly regulate the activity of c-di-GMP metabolic enzymes or alter the c-di-GMP level through other systems, while c-di-GMP can indirectly enhance or inhibit the hfq gene expression through intermediate factors. In this article, after briefly introducing the Hfq and c-di-GMP regulatory systems, we will focus on the direct and indirect regulation reported between Hfq and c-di-GMP, aiming to compare and link the two regulatory systems to further study the complicated physiological and metabolic systems of bacteria, and to lay a solid foundation for drawing a more complete global regulatory network.

Spatial organization enhances versatility and specificity in cyclic di-GMP signaling

2020 ◽  
Vol 401 (12) ◽  
pp. 1323-1334
Author(s):  
Sandra Kunz ◽  
Peter L. Graumann
Keyword(s):  
Protein Interactions ◽  
Cell Cycle Progression ◽  
Spatial Organization ◽  
Caulobacter Crescentus ◽  
Second Messenger ◽  
Protein Protein Interactions ◽  
Spatial Cues ◽  
Signaling Specificity ◽  
Regulatory Circuits ◽  
Second Messenger Signaling

AbstractThe second messenger cyclic di-GMP regulates a variety of processes in bacteria, many of which are centered around the decision whether to adopt a sessile or a motile life style. Regulatory circuits include pathogenicity, biofilm formation, and motility in a wide variety of bacteria, and play a key role in cell cycle progression in Caulobacter crescentus. Interestingly, multiple, seemingly independent c-di-GMP pathways have been found in several species, where deletions of individual c-di-GMP synthetases (DGCs) or hydrolases (PDEs) have resulted in distinct phenotypes that would not be expected based on a freely diffusible second messenger. Several recent studies have shown that individual signaling nodes exist, and additionally, that protein/protein interactions between DGCs, PDEs and c-di-GMP receptors play an important role in signaling specificity. Additionally, subcellular clustering has been shown to be employed by bacteria to likely generate local signaling of second messenger, and/or to increase signaling specificity. This review highlights recent findings that reveal how bacteria employ spatial cues to increase the versatility of second messenger signaling.

scholarly journals The Distinctive Regulation of Cyanobacterial Glutamine Synthetase

Life ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 52 ◽  
Author(s):  
Paul Bolay ◽  
M. Muro-Pastor ◽  
Francisco Florencio ◽  
Stephan Klähn
Keyword(s):  
Glutamine Synthetase ◽  
Gene Expression Regulation ◽  
Feedback Inhibition ◽  
Current Knowledge ◽  
Transcriptional Level ◽  
Distinctive Features ◽  
Small Proteins ◽  
Regulatory Systems ◽  
Covalent Modifications ◽  
Post Transcriptional Regulation

Glutamine synthetase (GS) features prominently in bacterial nitrogen assimilation as it catalyzes the entry of bioavailable nitrogen in form of ammonium into cellular metabolism. The classic example, the comprehensively characterized GS of enterobacteria, is subject to exquisite regulation at multiple levels, among them gene expression regulation to control GS abundance, as well as feedback inhibition and covalent modifications to control enzyme activity. Intriguingly, the GS of the ecologically important clade of cyanobacteria features fundamentally different regulatory systems to those of most prokaryotes. These include the interaction with small proteins, the so-called inactivating factors (IFs) that inhibit GS linearly with their abundance. In addition to this protein interaction-based regulation of GS activity, cyanobacteria use alternative elements to control the synthesis of GS and IFs at the transcriptional level. Moreover, cyanobacteria evolved unique RNA-based regulatory mechanisms such as glutamine riboswitches to tightly tune IF abundance. In this review, we aim to outline the current knowledge on the distinctive features of the cyanobacterial GS encompassing the overall control of its activity, sensing the nitrogen status, transcriptional and post-transcriptional regulation, as well as strain-specific differences.

scholarly journals Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins

2018 ◽  
Vol 115 (49) ◽  
pp. E11465-E11474 ◽  
Author(s):  
F. Donelson Smith ◽  
Mitchell H. Omar ◽  
Patrick J. Nygren ◽  
Joseph Soughayer ◽  
Naoto Hoshi ◽  
...  
Keyword(s):  
Solid Phase ◽  
Second Messenger ◽  
Nuclear Accumulation ◽  
Nucleotide Polymorphisms ◽  
Binding Assays ◽  
Subcellular Targeting ◽  
Regulatory Subunits ◽  
Anchoring Proteins ◽  
Anchoring Protein ◽  
Second Messenger Signaling

A-kinase anchoring proteins (AKAPs) shape second-messenger signaling responses by constraining protein kinase A (PKA) at precise intracellular locations. A defining feature of AKAPs is a helical region that binds to regulatory subunits (RII) of PKA. Mining patient-derived databases has identified 42 nonsynonymous SNPs in the PKA-anchoring helices of five AKAPs. Solid-phase RII binding assays confirmed that 21 of these amino acid substitutions disrupt PKA anchoring. The most deleterious side-chain modifications are situated toward C-termini of AKAP helices. More extensive analysis was conducted on a valine-to-methionine variant in the PKA-anchoring helix of AKAP18. Molecular modeling indicates that additional density provided by methionine at position 282 in the AKAP18γ isoform deflects the pitch of the helical anchoring surface outward by 6.6°. Fluorescence polarization measurements show that this subtle topological change reduces RII-binding affinity 8.8-fold and impairs cAMP responsive potentiation of L-type Ca2+ currents in situ. Live-cell imaging of AKAP18γ V282M-GFP adducts led to the unexpected discovery that loss of PKA anchoring promotes nuclear accumulation of this polymorphic variant. Targeting proceeds via a mechanism whereby association with the PKA holoenzyme masks a polybasic nuclear localization signal on the anchoring protein. This led to the discovery of AKAP18ε: an exclusively nuclear isoform that lacks a PKA-anchoring helix. Enzyme-mediated proximity-proteomics reveal that compartment-selective variants of AKAP18 associate with distinct binding partners. Thus, naturally occurring PKA-anchoring-defective AKAP variants not only perturb dissemination of local second-messenger responses, but also may influence the intracellular distribution of certain AKAP18 isoforms.

Recent Advances and Current Trends in Nucleotide Second Messenger Signaling in Bacteria

2019 ◽  
Vol 431 (5) ◽  
pp. 908-927 ◽  
Author(s):  
Regine Hengge ◽  
Susanne Häussler ◽  
Mihaela Pruteanu ◽  
Jörg Stülke ◽  
Natalia Tschowri ◽  
...  
Keyword(s):  
Second Messenger ◽  
Current Trends ◽  
Recent Advances ◽  
Second Messenger Signaling

scholarly journals Silence, Solitude, and Serotonin: Neural Mechanisms Linking Hearing Loss and Social Isolation

2020 ◽  
Vol 10 (6) ◽  
pp. 367
Author(s):  
Sarah M. Keesom ◽  
Laura M. Hurley
Keyword(s):  
Hearing Loss ◽  
Social Isolation ◽  
Human Subjects ◽  
Brain Regions ◽  
Neural Systems ◽  
Depression And Anxiety ◽  
Auditory Cognition ◽  
Regulatory Systems ◽  
Two Factors ◽  
And Function

For social animals that communicate acoustically, hearing loss and social isolation are factors that independently influence social behavior. In human subjects, hearing loss may also contribute to objective and subjective measures of social isolation. Although the behavioral relationship between hearing loss and social isolation is evident, there is little understanding of their interdependence at the level of neural systems. Separate lines of research have shown that social isolation and hearing loss independently target the serotonergic system in the rodent brain. These two factors affect both presynaptic and postsynaptic measures of serotonergic anatomy and function, highlighting the sensitivity of serotonergic pathways to both types of insult. The effects of deficits in both acoustic and social inputs are seen not only within the auditory system, but also in other brain regions, suggesting relatively extensive effects of these deficits on serotonergic regulatory systems. Serotonin plays a much-studied role in depression and anxiety, and may also influence several aspects of auditory cognition, including auditory attention and understanding speech in challenging listening conditions. These commonalities suggest that serotonergic pathways are worthy of further exploration as potential intervening mechanisms between the related conditions of hearing loss and social isolation, and the affective and cognitive dysfunctions that follow.

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