scholarly journals Intracellular cAMP signaling by soluble adenylyl cyclase

2011 ◽  
Vol 79 (12) ◽  
pp. 1277-1288 ◽  
Author(s):  
Martin Tresguerres ◽  
Lonny R. Levin ◽  
Jochen Buck
Keyword(s):  
Adenylyl Cyclase ◽  
Camp Signaling ◽  
Intracellular Camp ◽  
Soluble Adenylyl Cyclase

scholarly journals cAMP and Mitochondria

Physiology ◽  
2013 ◽  
Vol 28 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Federica Valsecchi ◽  
Lavoisier S. Ramos-Espiritu ◽  
Jochen Buck ◽  
Lonny R. Levin ◽  
Giovanni Manfredi
Keyword(s):  
Protein Phosphorylation ◽  
Adenylyl Cyclase ◽  
Regulatory Mechanism ◽  
Mitochondrial Proteins ◽  
Camp Signaling ◽  
Metabolic Adaptation ◽  
Mitochondrial Bioenergetics ◽  
Soluble Adenylyl Cyclase

Phosphorylation of mitochondrial proteins has emerged as a major regulatory mechanism for metabolic adaptation. cAMP signaling and PKA phosphorylation of mitochondrial proteins have just started to be investigated, and the presence of cAMP-generating enzymes and PKA inside mitochondria is still controversial. Here, we discuss the role of cAMP in regulating mitochondrial bioenergetics through protein phosphorylation and the evidence for soluble adenylyl cyclase as the source of cAMP inside mitochondria.

scholarly journals Spatial resolution of cAMP signaling by soluble adenylyl cyclase

2016 ◽  
Vol 214 (2) ◽  
pp. 125-127 ◽  
Author(s):  
Giusi Caldieri ◽  
Sara Sigismund
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Spatial Resolution ◽  
Camp Signaling ◽  
Receptor Signaling ◽  
Soluble Adenylyl Cyclase ◽  
Spatial Encoding ◽  
Cell Biol ◽  
G Protein Coupled

G protein–coupled receptor signaling starts at the plasma membrane and continues at endosomal stations. In this issue, Inda et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201512075) show that different forms of adenylyl cyclase are activated at the plasma membrane versus endosomes, providing a rationale for the spatial encoding of cAMP signaling.

scholarly journals Effect of Soluble Adenylyl Cyclase (ADCY10) Inhibitors on the LH-Stimulated cAMP Synthesis in Mltc-1 Leydig Cell Line

2021 ◽  
Vol 22 (9) ◽  
pp. 4641
Author(s):  
Thi Mong Diep Nguyen ◽  
Laura Filliatreau ◽  
Danièle Klett ◽  
Nong Van Hai ◽  
Nguyen Thuy Duong ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Leydig Cells ◽  
Intracellular Camp ◽  
Camp Accumulation ◽  
Adenylyl Cyclases ◽  
High Concentration ◽  
Soluble Adenylyl Cyclase ◽  
Bicarbonate Ions ◽  
Intracellular Camp Accumulation

In contrast to all transmembrane adenylyl cyclases except ADCY9, the cytosolic soluble adenylyl cyclase (ADCY10) is insensitive to forskolin stimulation and is uniquely modulated by calcium and bicarbonate ions. In the present paper, we focus on ADCY10 localization and a kinetic analysis of intracellular cAMP accumulation in response to human LH in the absence or presence of four different ADCY10 inhibitors (KH7, LRE1, 2-CE and 4-CE) in MTLC-1 cells. ADCY10 was immuno-detected in the cytoplasm of MLTC-1 cells and all four inhibitors were found to inhibit LH-stimulated cAMP accumulation and progesterone level in MLTC-1 and testosterone level primary Leydig cells. Interestingly, similar inhibitions were also evidenced in mouse testicular Leydig cells. In contrast, the tmAC-specific inhibitors ddAdo3′ and ddAdo5′, even at high concentration, exerted weak or no inhibition on cAMP accumulation, suggesting an important role of ADCY10 relative to tmACs in the MLTC-1 response to LH. The strong synergistic effect of HCO3− under LH stimulation further supports the involvement of ADCY10 in the response to LH.

scholarly journals Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells

2012 ◽  
Vol 302 (6) ◽  
pp. C839-C852 ◽  
Author(s):  
Wei P. Feinstein ◽  
Bing Zhu ◽  
Silas J. Leavesley ◽  
Sarah L. Sayner ◽  
Thomas C. Rich
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Microvascular Endothelial Cells ◽  
Camp Production ◽  
Barrier Integrity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Camp Signaling Pathway ◽  
Microvascular Endothelial

Cyclic AMP signals encode information required to differentially regulate a wide variety of cellular responses; yet it is not well understood how information is encrypted within these signals. An emerging concept is that compartmentalization underlies specificity within the cAMP signaling pathway. This concept is based on a series of observations indicating that cAMP levels are distinct in different regions of the cell. One such observation is that cAMP production at the plasma membrane increases pulmonary microvascular endothelial barrier integrity, whereas cAMP production in the cytosol disrupts barrier integrity. To better understand how cAMP signals might be compartmentalized, we have developed mathematical models in which cellular geometry as well as total adenylyl cyclase and phosphodiesterase activities were constrained to approximate values measured in pulmonary microvascular endothelial cells. These simulations suggest that the subcellular localizations of adenylyl cyclase and phosphodiesterase activities are by themselves insufficient to generate physiologically relevant cAMP gradients. Thus, the assembly of adenylyl cyclase, phosphodiesterase, and protein kinase A onto protein scaffolds is by itself unlikely to ensure signal specificity. Rather, our simulations suggest that reductions in the effective cAMP diffusion coefficient may facilitate the formation of substantial cAMP gradients. We conclude that reductions in the effective rate of cAMP diffusion due to buffers, structural impediments, and local changes in viscosity greatly facilitate the ability of signaling complexes to impart specificity within the cAMP signaling pathway.

Two domains are critical for the nuclear localization of soluble adenylyl cyclase

Biochimie ◽  
2006 ◽  
Vol 88 (3-4) ◽  
pp. 319-328 ◽  
Author(s):  
Q FENG ◽  
Y ZHANG ◽  
Y LI ◽  
Z LIU ◽  
J ZUO ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Nuclear Localization ◽  
Soluble Adenylyl Cyclase

scholarly journals Non-canonical regulation of glycogenolysis and the Warburg phenotype by soluble adenylyl cyclase

2020 ◽  
Author(s):  
Jung-Chin Chang ◽  
Simei Go ◽  
Eduardo H. Gilglioni ◽  
Hang Lam Li ◽  
Hsu-Li Huang ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Adenylyl Cyclase ◽  
Energy Homeostasis ◽  
Aerobic Glycolysis ◽  
Glycogen Metabolism ◽  
Adenylyl Cyclases ◽  
Soluble Adenylyl Cyclase ◽  
Atp Level ◽  
Downstream Effectors ◽  
Different Types

AbstractCyclic AMP is produced in cells by two very different types of adenylyl cyclases: the canonical transmembrane adenylyl cyclases (tmACs, ADCY1∼9) and the evolutionarily more conserved soluble adenylyl cyclase (sAC, ADCY10). While the role and regulation of tmACs is well documented, much less is known of sAC in cellular metabolism. We demonstrate here that sAC is an acute regulator of glycolysis, oxidative phosphorylation and glycogen metabolism, tuning their relative bioenergetic contributions. Suppression of sAC activity leads to aerobic glycolysis, enhanced glycogenolysis, decreased oxidative phosphorylation, and an elevated cytosolic NADH/NAD+ ratio, resembling the Warburg phenotype. Importantly, we found that glycogen metabolism is regulated in opposite directions by cAMP depending on its location of synthesis and downstream effectors. While the canonical tmAC-cAMP-PKA axis promotes glycogenolysis, we identify a novel sAC-cAMP-Epac1 axis that suppresses glycogenolysis. These data suggest that sAC is an autonomous bioenergetic sensor that suppresses aerobic glycolysis and glycogenolysis when ATP levels suffice. When the ATP level falls, diminished sAC activity induces glycogenolysis and aerobic glycolysis to maintain energy homeostasis.

scholarly journals Pharmacological and genetic activation of cAMP synthesis disrupts cholesterol utilization in Mycobacterium tuberculosis

2021 ◽  
Author(s):  
Kaley M. Wilburn ◽  
Christine R. Montague ◽  
Bo Qin ◽  
Ashley K. Woods ◽  
Melissa S. Love ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Adenylyl Cyclase ◽  
Cholesterol Metabolism ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Signaling ◽  
Camp Synthesis ◽  
Pharmacokinetic Properties ◽  
Bacterial Utilization

There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics that can disrupt cholesterol utilization by Mtb in vivo. Here we identify a novel small molecule agonist (V-59) of the Mtb adenylyl cyclase Rv1625c, which stimulates 3’, 5’-cyclic adenosine monophosphate (cAMP) synthesis and inhibits cholesterol utilization by Mtb. Similarly, using a complementary genetic approach that induces bacterial cAMP synthesis independent of Rv1625c, we demonstrate that inducing cAMP synthesis is sufficient to inhibit cholesterol utilization in Mtb. Although the physiological roles of individual adenylyl cyclase enzymes in Mtb are largely unknown, here we demonstrate that the transmembrane region of Rv1625c is required for cholesterol metabolism. Finally, in this work the pharmacokinetic properties of Rv1625c agonists are optimized, producing an orally-available Rv1625c agonist that impairs Mtb pathogenesis in infected mice. Collectively, this work demonstrates a novel role for Rv1625c and cAMP signaling in controlling cholesterol metabolism in Mtb and establishes that cAMP signaling can be pharmacologically manipulated for the development of new antibiotic strategies.

Sign in / Sign up

Export Citation Format

Share Document