scholarly journals Diurnal metabolic control in cyanobacteria requires perception of second messenger signaling molecule c-di-AMP by the carbon control protein SbtB

2021 ◽  
Vol 7 (50) ◽  
Author(s):  
Khaled A. Selim ◽  
Michael Haffner ◽  
Markus Burkhardt ◽  
Oliver Mantovani ◽  
Niels Neumann ◽  
...  
Keyword(s):  
Metabolic Control ◽  
Second Messenger ◽  
Signaling Molecule ◽  
Second Messenger Signaling ◽  
Carbon Control ◽  
Control Protein

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 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 Yin and Yang of Biofilm Formation and Cyclic di-GMP Signaling of the Gastrointestinal Pathogen Salmonella enterica Serovar Typhimurium

2021 ◽  
pp. 1-18
Author(s):  
Agaristi Lamprokostopoulou ◽  
Ute Römling
Keyword(s):  
Biofilm Formation ◽  
Second Messenger ◽  
Bacterial Biofilm ◽  
Chronic Infections ◽  
Nutrient Sources ◽  
Microbial Biofilms ◽  
Extracellular Signaling ◽  
Serovar Typhimurium ◽  
Yin And Yang ◽  
Second Messenger Signaling

Within the last 60 years, microbiological research has challenged many dogmas such as bacteria being unicellular microorganisms directed by nutrient sources; these investigations produced new dogmas such as cyclic diguanylate monophosphate (cyclic di-GMP) second messenger signaling as a ubiquitous regulator of the fundamental sessility/motility lifestyle switch on the single-cell level. Successive investigations have not yet challenged this view; however, the complexity of cyclic di-GMP as an intracellular bacterial signal, and, less explored, as an extracellular signaling molecule in combination with the conformational flexibility of the molecule, provides endless opportunities for cross-kingdom interactions. Cyclic di-GMP-directed microbial biofilms commonly stimulate the immune system on a lower level, whereas host-sensed cyclic di-GMP broadly stimulates the innate and adaptive immune responses. Furthermore, while the intracellular second messenger cyclic di-GMP signaling promotes bacterial biofilm formation and chronic infections, oppositely, <i>Salmonella</i> Typhimurium cellulose biofilm inside immune cells is not endorsed. These observations only touch on the complexity of the interaction of biofilm microbial cells with its host. In this review, we describe the Yin and Yang interactive concepts of biofilm formation and cyclic di-GMP signaling using <i>S</i>. Typhimurium as an example.

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