<i>Synechocystis</i>
            Strain PCC 6803
            <i>cya</i>
            2, a Prokaryotic Gene That Encodes a Guanylyl Cyclase

Alda, Jesús A. G. Ochoa de; Ajlani, Ghada; Houmard, Jean

doi:10.1128/jb.182.13.3839-3842.2000

Cited by 56 publications

(41 citation statements)

References 32 publications

(37 reference statements)

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“…Furthermore, a variety of other ligands have been reported for GAF domains in proteins other than PDEs (56), fostering such a speculation on other small molecule PDE regulators acting through the GAF domains. On the other hand, cGMP was long assumed not to exist in prokaryotes, but it was recently identified in cyanobacteria (60,61), which are assumed to have a common progenitor with mammalian mitochondria (62). It is tempting to speculate that both second messengers, cGMP and cAMP, might be conserved in this organelle, but it remains an exciting question.…”

Section: Discussionmentioning

confidence: 99%

A Phosphodiesterase 2A Isoform Localized to Mitochondria Regulates Respiration

Acı́n-Pérez

Russwurm

Günnewig

et al. 2011

Journal of Biological Chemistry

119

133

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Mitochondria are central organelles in cellular energy metabolism, apoptosis, and aging processes. A signaling network regulating these functions was recently shown to include soluble adenylyl cyclase as a local source of the second messenger cAMP in the mitochondrial matrix. However, a mitochondrial cAMPdegrading phosphodiesterase (PDE) necessary for switching off this cAMP signal has not yet been identified. Here, we describe the identification and characterization of a PDE2A isoform in mitochondria from rodent liver and brain. We find that mitochondrial PDE2A is located in the matrix and that the unique N terminus of PDE2A isoform 2 specifically leads to mitochondrial localization of this isoform. Functional assays show that mitochondrial PDE2A forms a local signaling system with soluble adenylyl cyclase in the matrix, which regulates the activity of the respiratory chain. Our findings complete a cAMP signaling cascade in mitochondria and have implications for understanding the regulation of mitochondrial processes and for their pharmacological modulation.Mitochondria play central roles in cellular energy metabolism, as well as in the regulation of cell cycle progression, apoptosis, and aging processes (1, 2). Despite their importance, signaling into, from, and within mitochondria is still not well understood. Emerging signaling mechanisms in mitochondria and between the organelle and its environment include reversible protein deacetylation (3, 4), redox regulation and reactive oxygen species formation (5-7), and cyclic adenosine monophosphate (cAMP) signaling (8, 9).cAMP-dependent effects and proteins of cAMP signaling systems, such as cAMP-responsive element-binding protein (CREB), protein kinase A (PKA), and A-kinase anchoring proteins (AKAPs), 3 have been described in mitochondria (10 -12). In addition to these effector proteins, a complete cAMP signaling microdomain requires enzymes for synthesis and degradation of the second messenger. Although an intramitochondrial cAMP source has been identified recently (8), there is no known cAMP-degrading enzyme in this organelle. Cyclic AMP is formed inside mitochondria by soluble adenylyl cyclase (sAC) (8), a member of Class III of the nucleotidyl cyclase family, which also comprises the G-protein-regulated transmembrane adenylyl cyclases (13). Unique from transmembrane adenylyl cyclases, sAC is activated by bicarbonate (14), and it appears to act as a metabolic sensor (15), whose mitochondrial form(s) seems to modulate PKA-mediated regulation of respiration (8) and apoptosis (16).The opponents of the cyclic nucleotide-forming cyclases are cyclic nucleotide monophosphate (cNMP)-degrading phosphodiesterases (PDEs). Mammalian cells contain a varying subset of members of the classical PDE family, which comprises 11 PDE gene families (PDE1-11) (17, 18) and non-generic PDEs such as the protein human Prune (19,20). The isoforms of the generic PDEs comprise homologous catalytic domains, fused to varying regulatory domains, making them sensitive to a variety of signals s...

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Section: Discussionmentioning

confidence: 99%

A Phosphodiesterase 2A Isoform Localized to Mitochondria Regulates Respiration

Acı́n-Pérez

Russwurm

Günnewig

et al. 2011

Journal of Biological Chemistry

119

133

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“…the control of Streptomycetes development by c-di-GMP (6)) reveal that the cellular functions of second messengers, even of well studied signaling molecules like c-di-GMP, are not yet fully explored. Moreover, some bacteria, such as the cyanobacterium Synechocystis PCC6803, are capable of producing the cyclic nucleotide cGMP (7). However, although the cyclase that synthesizes cGMP has been biochemically and structurally characterized, the physiological role of the nucleotide remains to be elucidated (8).…”

mentioning

confidence: 99%

Structural and Biochemical Analysis of the Essential Diadenylate Cyclase CdaA from Listeria monocytogenes

Rosenberg

Dickmanns

Neumann

et al. 2015

Journal of Biological Chemistry

121

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“…In bacteria, cAMP has a role in alleviating glucose catabolite repression (23,40), and cGMP has been shown to act as a signaling molecule in Synechocystis cyanobacteria (41,42). Another novel guanosine nucleotide, the cyclic dinucleotide GMP (c-di-GMP; cyclic diguanylate [3Ј,5Ј-cyclic diguanylic acid], cGpGp) ( Fig.…”

mentioning

confidence: 99%

c-di-GMP (3′-5′-Cyclic Diguanylic Acid) Inhibits Staphylococcus aureus Cell-Cell Interactions and Biofilm Formation

Karaolis¹,

Rashid²,

Rajanna³

et al. 2005

Antimicrob Agents Chemother

134

101

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Staphylococcus aureus is an important pathogen of humans and animals, and antibiotic resistance is a public health concern. Biofilm formation is essential in virulence and pathogenesis, and the ability to resist antibiotic treatment results in difficult-to-treat and persistent infections. As such, novel antimicrobial approaches are of great interest to the scientific, medical, and agriculture communities. We recently proposed that modulating levels of the cyclic dinucleotide signaling molecule, c-di-GMP (cyclic diguanylate [3,5-cyclic diguanylic acid], cGpGp), has utility in regulating phenotypes of prokaryotes. We report that extracellular c-di-GMP shows activity against human clinical and bovine intramammary mastitis isolates of S. aureus, including methicillinresistant S. aureus (MRSA) isolates. We show that chemically synthesized c-di-GMP is soluble and stable in water and physiological saline and stable following boiling and exposure to acid and alkali. Treatment of S. aureus with extracellular c-di-GMP inhibited cell-to-cell (intercellular) adhesive interactions in liquid medium and reduced (>50%) biofilm formation in human and bovine isolates compared to untreated controls. c-di-GMP inhibited the adherence of S. aureus to human epithelial HeLa cells. The cyclic nucleotide analogs cyclic GMP and cyclic AMP had a lesser inhibitory effect on biofilms, while 5-GMP had no major effect. We propose that cyclic dinucleotides such as c-di-GMP, used either alone or in combination with other antimicrobial agents, represent a novel and attractive approach in the development of intervention strategies for the prevention of biofilms and the control and treatment of infection.

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Synechocystis Strain PCC 6803 cya 2, a Prokaryotic Gene That Encodes a Guanylyl Cyclase

Cited by 56 publications

References 32 publications

A Phosphodiesterase 2A Isoform Localized to Mitochondria Regulates Respiration

A Phosphodiesterase 2A Isoform Localized to Mitochondria Regulates Respiration

Structural and Biochemical Analysis of the Essential Diadenylate Cyclase CdaA from Listeria monocytogenes

c-di-GMP (3′-5′-Cyclic Diguanylic Acid) Inhibits Staphylococcus aureus Cell-Cell Interactions and Biofilm Formation

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