scholarly journals c-di-AMP hydrolysis by a novel type of phosphodiesterase promotes differentiation of multicellular bacteria

2019 ◽  
Author(s):  
Andreas Latoscha ◽  
David Jan Drexler ◽  
Mahmoud M. Al-Bassam ◽  
Volkhard Kaever ◽  
Kim C. Findlay ◽  
...  

ABSTRACTAntibiotic-producing Streptomyces use the diadenylate cyclase DisA to synthesize the nucleotide second messenger c-di-AMP but the mechanism for terminating c-di-AMP signaling and the proteins that bind the molecule to effect signal transduction are unknown. Here, we identify the AtaC protein as a new type of c-di-AMP-specific phosphodiesterase that is also conserved in pathogens such as Streptococcus pneumoniae and Mycobacterium tuberculosis. AtaC is monomeric in solution and binds Mn2+ to specifically hydrolyze c-di-AMP to AMP via the intermediate 5’-pApA. As an effector of c-di-AMP signaling, we characterize the RCK-domain protein CpeA as the first c-di-AMP-binding protein to be identified in Streptomyces. CpeA interacts with the predicted cation / proton antiporter, CpeB, linking c-di-AMP signaling to ion homeostasis in actinobacteria. Hydrolysis of c-di-AMP is critical for normal growth and differentiation in Streptomyces, connecting osmotic stress to development. Thus, we present the discovery of two novel components of c-di-AMP signaling in bacteria and show that precise control of this second messenger is essential for osmoregulation and coordinated development in Streptomyces.

2020 ◽  
Vol 117 (13) ◽  
pp. 7392-7400 ◽  
Author(s):  
Andreas Latoscha ◽  
David Jan Drexler ◽  
Mahmoud M. Al-Bassam ◽  
Adrian M. Bandera ◽  
Volkhard Kaever ◽  
...  

Antibiotic-producing Streptomyces use the diadenylate cyclase DisA to synthesize the nucleotide second messenger c-di-AMP, but the mechanism for terminating c-di-AMP signaling and the proteins that bind the molecule to effect signal transduction are unknown. Here, we identify the AtaC protein as a c-di-AMP-specific phosphodiesterase that is also conserved in pathogens such as Streptococcus pneumoniae and Mycobacterium tuberculosis. AtaC is monomeric in solution and binds Mn2+ to specifically hydrolyze c-di-AMP to AMP via the intermediate 5′-pApA. As an effector of c-di-AMP signaling, we characterize the RCK_C domain protein CpeA. c-di-AMP promotes interaction between CpeA and the predicted cation/proton antiporter, CpeB, linking c-di-AMP signaling to ion homeostasis in Actinobacteria. Hydrolysis of c-di-AMP is critical for normal growth and differentiation in Streptomyces, connecting ionic stress to development. Thus, we present the discovery of two components of c-di-AMP signaling in bacteria and show that precise control of this second messenger is essential for ion balance and coordinated development in Streptomyces.


2005 ◽  
Vol 138 (4) ◽  
pp. 2048-2060 ◽  
Author(s):  
Ning-Hui Cheng ◽  
Jon K. Pittman ◽  
Toshiro Shigaki ◽  
Jinesh Lachmansingh ◽  
Sherry LeClere ◽  
...  

1989 ◽  
Vol 9 (1) ◽  
pp. 152-158
Author(s):  
H A Fujimura

I have isolated a new type of sterile mutant of Saccharomyces cerevisiae, carrying a single mutant allele, designated dac1, which was mapped near the centromere on chromosome VIII. The dac1 mutation caused specific defects in the pheromone responsiveness of both a and alpha cells and did not seem to be associated with any pleiotropic phenotypes. Thus, in contrast to the ste4, ste5, ste7, ste11, and ste12 mutations, the dac1 mutation had no significant effect on such constitutive functions of haploid cells as pheromone production and alpha-factor destruction. The characteristics of this phenotype suggest that the DAC1 gene encodes a component of the pheromone response pathway common to both a and alpha cells. Introduction of the GPA1 gene encoding an S. cerevisiae homolog of the alpha subunit of mammalian guanine nucleotide-binding regulatory proteins (G proteins) into sterile dac1 mutants resulted in restoration of pheromone responsiveness and mating competence to both a and alpha cells. These results suggest that the dac1 mutation is an allele of the GPA1 gene and thus provide genetic evidence that the yeast G protein homolog is directly involved in the mating pheromone signal transduction pathway.


1998 ◽  
Vol 275 (5) ◽  
pp. C1277-C1283 ◽  
Author(s):  
Martin Wilding ◽  
Gian Luigi Russo ◽  
Anthony Galione ◽  
Marcella Marino ◽  
Brian Dale

We report an ion channel in the plasma membrane of unfertilized oocytes of the ascidian Ciona intestinalis that is directly gated by the second messenger ADP-ribose. The ion channel is permeable to Ca2+ and Na+ and is characterized by a reversal potential between 0 and +20 mV and a unitary conductance of 140 pS. Preinjection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA) or antagonists of intracellular Ca2+ release channels into oocytes did not inhibit the ADP-ribose current, demonstrating that the channel is activated in a Ca2+-independent manner. Both the fertilization current and the current induced by the injection of nicotinamide nucleotides are blocked by nicotinamide, suggesting that the ADP-ribose channel is activated at fertilization in a nicotinamide-sensitive manner. These data suggest that ascidian sperm trigger the hydrolysis of nicotinamide nucleotides in the oocyte to ADP-ribose and that this mechanism is responsible for the production of the fertilization current.


Atmosphere ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 652 ◽  
Author(s):  
Bin Jiang ◽  
Lei Ding ◽  
Xuejuan Fang

Exploring the coordinated development of urbanization (U), technology innovation (T), and the atmospheric environment (A) is an important way to realize the sustainable development of new-type urbanization in China. Compared with existing research, we developed an integrated index system that accurately represents the overall effect of the three subsystems of UTA, and a new weight determination method, the structure entropy weight (SEW), was introduced. Then, we constructed a coordinated development index (CDI) of UTA to measure the level of sustainability of new-type urbanization. This study also analyzed trends observed in UTA for 11 cities in Zhejiang Province of China, using statistical panel data collected from 2006 to 2017. The results showed that: (1) urbanization efficiency, the benefits of technological innovation, and air quality weigh the most in the indicator systems, which indicates that they are key factors in the behavior of UTA. The subsystem scores of the 11 cities show regional differences to some extent. (2) Comparing the coordination level of UTA subsystems, we found that the order is: coordination degree of UT > coordination degree of UA > coordination degree of TA. This suggests that the atmospheric environment system improvement is an important strategic decision for sustainable urbanization in Zhejiang. (3) The UTACDI values of the 11 cities are not high enough, as the coordination is mainly low, basic, or good, while none of the cities reached the stage of excellent coordination. (4) Gray Model (1,1) revealed that the time taking to achieve excellent coordination varies for different cities. Hangzhou and Ningbo were predicted to reach the excellent coordination level in 2018. Other cities are predicted to take 2–4 years to adjust their urbanization strategies enough to be considered to have excellent coordination of their UTA system.


1995 ◽  
Vol 132 (5) ◽  
pp. 523-531 ◽  
Author(s):  
Edward M Brown ◽  
Martin Pollak ◽  
Steven C Hebert

Brown EM, Pollak M, Hebert SC. Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells. Eur J Endocrinol 1995;132:523–31. ISSN 0804–4643 Mineral ion homeostasis in mammalian species is maintained by a complex mechanism comprising sensors of the extracellular calcium concentration (Ca02+) (i.e. parathyroid cells) as well as effectors that modify their translocation of mineral ions into and out of the extracellular fluid (e.g. kidney) in response to calciotropic hormones. Indirect evidence accumulated over the past decade suggested that parathyroid cells sense Ca02+ through a cell surface receptor coupled to intracellular second messenger systems via one or more guanine nucleotide regulatory (G) proteins. More recently, Brown et al. employed expression cloning in Xenopus laevis oocytes to isolate a cDNA encoding a Ca02+-sensing receptor from bovine parathyroid. The expressed receptor activates phospholipase C in a G-protein dependent manner and shows pharmacological properties almost identical to those of the native parathyroid receptor. Agonists for the receptor include not only divalent cations (e.g. Ca2+ and Mg2+) but also trivalent cations and even organic polycations such as neomycin. The deduced amino acid sequence of the cloned receptor confirms that it is a member of the superfamily of G-protein-coupled receptors. Receptor transcripts are present in parathyroid as well as in kidney, thyroid and brain. Therefore, this receptor may mediate the sensing of Ca02+ not only by parathyroid cells but also by other tissues directly regulated by Ca02+ (e.g. the thyroidal C cells and certain kidney cells) as well as those not currently known to be involved in calcium homeostasis (viz. in the brain). Further evidence for the physiological relevance of the receptor comes from the discovery that mutations in the human homolog of the Ca02+-sensing receptor gene cause three inherited disorders of mineral ion homeostasis. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are the clinical expression of inactivating mutations of the receptor when present in the heterozygous and homozygous state, respectively. An autosomal dominant form of hypocalcemia, on the other hand, results from an activating mutation of the receptor. Thus, this Ca02+-sensing receptor permits Ca02+ to act, in effect, as an extracellular first messenger in addition to its more widely recognized role as an intracellular second messenger. Edward M Brown, Endocrine–Hypertension Division, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA02115, USA


Sign in / Sign up

Export Citation Format

Share Document