scholarly journals Role of soluble adenylyl cyclase in the heart

2012 ◽  
Vol 302 (3) ◽  
pp. H538-H543 ◽  
Author(s):  
Jonathan Chen ◽  
Lonny R. Levin ◽  
Jochen Buck
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Nutrient Utilization ◽  
Soluble Adenylyl Cyclase ◽  
Atp Production ◽  
Downstream Effector ◽  
Subsequent Activation ◽  
Unique Source

This review discusses the potential place of soluble adenylyl cyclase (sAC) in the framework of signaling in the cardiovascular system. cAMP has been studied as a critical and pleiotropic second messenger in cardiomyocytes, endothelial cells, and smooth muscle vascular cells for many years. It is involved in the transduction of signaling by catecholamines, prostaglandins, adenosine, and glucagon, just to name a few. These hormones can act via cAMP by binding to a G protein-coupled receptor on the plasma membrane with subsequent activation of a heterotrimeric G protein and its downstream effector, transmembrane adenylyl cyclase. This has long been the canonical standard for cAMP production in a cell. However, the relatively recent discovery of a unique source of cAMP, sAC, creates the potential for a shift in this signaling paradigm. In fact, sAC has been shown to play a role in apoptosis in coronary endothelial cells and cardiomyocytes. Additionally, it links nutrient utilization with ATP production in the liver and brain, which suggests one of many potential roles for sAC in cardiac function. The possibility of producing cAMP from a source distal to the plasma membrane provides a critical new building block for reconstructing the cellular signaling infrastructure.

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 High level expression of transfected G protein αi3subunit is required for plasma membrane targeting and adenylyl cyclase inhibition in NIH 3T3 fibroblasts

FEBS Letters ◽  
1992 ◽  
Vol 312 (2-3) ◽  
pp. 223-228 ◽  
Author(s):  
Sylvie Hermouet ◽  
Philippe de Mazancourt ◽  
Allen M. Spiegel ◽  
Marilyn Gist Farquhar ◽  
Bridget S. Wilson
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Membrane Targeting ◽  
High Level Expression ◽  
3T3 Fibroblasts ◽  
High Level ◽  
Nih 3T3

scholarly journals G protein-regulated endocytic trafficking of adenylyl cyclase type 9

2020 ◽  
Author(s):  
André M. Lazar ◽  
Roshanak Irannejad ◽  
Tanya A. Baldwin ◽  
Aparna A. Sundaram ◽  
J. Silvio Gutkind ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Subcellular Location ◽  
Endocytic Pathway ◽  
Heterotrimeric G Proteins ◽  
Camp Production ◽  
Stimulation Of

SummaryGPCRs are increasingly recognized to initiate signaling via heterotrimeric G proteins as they move through the endocytic network, but little is known about how relevant G protein effectors are localized. Here we report dynamic trafficking of adenylyl cyclase type 9 (AC9) from the plasma membrane to endosomes, while adenylyl cyclase type 1 (AC1) remains in the plasma membrane, and stimulation of AC9 trafficking by ligand-induced activation of Gs-coupled GPCRs or Gs. AC9 transits a similar dynamin-dependent early endocytic pathway as activated GPCRs but, in contrast to GPCR trafficking which is regulated by β-arrestin but not Gs, AC9 trafficking is regulated by Gs but not β-arrestin. We also show that AC9, but not AC1, contributes to cAMP production from endosomes. These results reveal dynamic and isoform-specific trafficking of adenylyl cyclase in the endocytic network, and a discrete role of a heterotrimeric G protein in controlling subcellular location of a relevant effector.

scholarly journals Adenylyl cyclases (ACs) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Carmen W. Dessauer ◽  
Rennolds Ostrom ◽  
Roland Seifert ◽  
Val J. Watts
Keyword(s):  
Cyclic Amp ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Adenylyl Cyclases ◽  
Adenylyl Cyclase Activity ◽  
Α Subunit ◽  
Soluble Adenylyl Cyclase ◽  
Catalytic Domains ◽  
Stimulatory G Protein ◽  
Membrane Spanning

Adenylyl cyclase, E.C. 4.6.1.1, converts ATP to cyclic AMP and pyrophosphate. Mammalian membrane-delimited adenylyl cyclases (nomenclature as approved by the NC-IUPHAR Subcommittee on Adenylyl cyclases [9]) are typically made up of two clusters of six TM domains separating two intracellular, overlapping catalytic domains that are the target for the nonselective activators Gαs (the stimulatory G protein α subunit) and forskolin (except AC9, [21]). adenosine and its derivatives (e.g. 2',5'-dideoxyadenosine), acting through the P-site,are inhibitors of adenylyl cyclase activity [27]. Four families of membranous adenylyl cyclase are distinguishable: calmodulin-stimulated (AC1, AC3 and AC8), Ca2+- and Gβγ-inhibitable (AC5, AC6 and AC9), Gβγ-stimulated and Ca2+-insensitive (AC2, AC4 and AC7), and forskolin-insensitive (AC9) forms. A soluble adenylyl cyclase (AC10) lacks membrane spanning regions and is insensitive to G proteins.It functions as a cytoplasmic bicarbonate (pH-insensitive) sensor [5].

scholarly journals Organization of G Proteins and Adenylyl Cyclase at the Plasma Membrane

1997 ◽  
Vol 8 (12) ◽  
pp. 2365-2378 ◽  
Author(s):  
Chunfa Huang ◽  
John R. Hepler ◽  
Linda T. Chen ◽  
Alfred G. Gilman ◽  
Richard G.W. Anderson ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Buoyant Density ◽  
Cyclase Activity ◽  
Immunogold Electron Microscopy ◽  
Adenylyl Cyclase Activity ◽  
A Cell ◽  
Hormone Sensitive ◽  
Punctate Pattern

There is mounting evidence for the organization and compartmentation of signaling molecules at the plasma membrane. We find that hormone-sensitive adenylyl cyclase activity is enriched in a subset of regulatory G protein-containing fractions of the plasma membrane. These subfractions resemble, in low buoyant density, structures of the plasma membrane termed caveolae. Immunofluorescence experiments revealed a punctate pattern of G protein α and β subunits, consistent with concentration of these proteins at distinct sites on the plasma membrane. Partial coincidence of localization of G protein α subunits with caveolin (a marker for caveolae) was observed by double immunofluorescence. Results of immunogold electron microscopy suggest that some G protein is associated with invaginated caveolae, but most of the protein resides in irregular structures of the plasma membrane that could not be identified morphologically. Because regulated adenylyl cyclase activity is present in low-density subfractions of plasma membrane from a cell type (S49 lymphoma) that does not express caveolin, this protein is not required for organization of the adenylyl cyclase system. The data suggest that hormone-sensitive adenylyl cyclase systems are localized in a specialized subdomain of the plasma membrane that may optimize the efficiency and fidelity of signal transduction.

scholarly journals Soluble adenylyl cyclase mediates bicarbonate-dependent corneal endothelial cell protection

2011 ◽  
Vol 300 (2) ◽  
pp. C368-C374 ◽  
Author(s):  
Shimin Li ◽  
Kah Tan Allen ◽  
Joseph A. Bonanno
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Annexin V ◽  
Camp Response Element Binding ◽  
Cell Protection ◽  
Cytochrome C Release ◽  
Soluble Adenylyl Cyclase ◽  
Cellular Protection ◽  
Element Binding Protein ◽  
Nonlinear Relation

Cyclic AMP produced from membrane receptor complex bound adenylyl cyclases is protective in corneal endothelial cells (CEC). CEC also express soluble adenylyl cyclase (sAC), which is localized throughout the cytoplasm. When activated by HCO3−, cAMP concentration ([cAMP]) increases by ∼50%. Here we ask if cAMP produced from sAC is also protective. We examined the effects of HCO3−, pH, phosphodiesterase 4 inhibition by rolipram, sAC inhibition by 2HE (2-hydroxyestradiol), and sAC small interfering RNA (siRNA) knockdown on basal and staurosporine-mediated apoptosis. HCO3− (40 mM) or 50 μM rolipram raised [cAMP] to similar levels and protected endothelial cells by 50% relative to a HCO3−-free control, whereas 2HE, which decreased [cAMP] by 40%, and H89 (PKA inhibitor) doubled the apoptotic rate. sAC expression was reduced by two-thirds in the absence of HCO3− and was reduced to 15% of control by sAC siRNA. Protection by HCO3− was eliminated in siRNA-treated cells. Similarly, caspase-3 activity and cytochrome c release were reduced by HCO3− and enhanced by 2HE or siRNA. Analysis of percent annexin V+ cells as a function of [cAMP] revealed an inverse, nonlinear relation, suggesting a protective threshold [cAMP] of 10 pmol/mg protein. Relative levels of phosphorylated cAMP response element binding protein and phosphorylated Bcl-2 were decreased in CEC treated with 2HE or siRNA, suggesting that HCO3−-dependent endogenous sAC activity can mobilize antiapoptotic signal transduction. Overall, our data suggest a new role for sAC in endogenous cellular protection.

Salt-induced Na+/K+-ATPase-α/β expression involves soluble adenylyl cyclase in endothelial cells

2017 ◽  
Vol 469 (10) ◽  
pp. 1401-1412 ◽  
Author(s):  
Mirja Mewes ◽  
Johanna Nedele ◽  
Katrin Schelleckes ◽  
Olga Bondareva ◽  
Malte Lenders ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Soluble Adenylyl Cyclase

scholarly journals G protein-regulated endocytic trafficking of adenylyl cyclase type 9

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
André M Lazar ◽  
Roshanak Irannejad ◽  
Tanya A Baldwin ◽  
Aparna B Sundaram ◽  
J Silvio Gutkind ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Traffic Control ◽  
Receptor Activation ◽  
Endocytic Pathway ◽  
Heterotrimeric G Proteins ◽  
Stimulation Of

GPCRs are increasingly recognized to initiate signaling via heterotrimeric G proteins as they move through the endocytic network, but little is known about how relevant G protein effectors are localized. Here we report selective trafficking of adenylyl cyclase type 9 (AC9) from the plasma membrane to endosomes while adenylyl cyclase type 1 (AC1) remains in the plasma membrane, and stimulation of AC9 trafficking by ligand-induced activation of Gs-coupled GPCRs. AC9 transits a similar, dynamin-dependent early endocytic pathway as ligand-activated GPCRs. However, unlike GPCR traffic control which requires β-arrestin but not Gs, AC9 traffic control requires Gs but not β-arrestin. We also show that AC9, but not AC1, mediates cAMP production stimulated by endogenous receptor activation in endosomes. These results reveal dynamic and isoform-specific trafficking of adenylyl cyclase in the endocytic network, and a discrete role of a heterotrimeric G protein in regulating the subcellular distribution of a relevant effector.

scholarly journals Soluble Adenylyl Cyclase Controls Mitochondria-dependent Apoptosis in Coronary Endothelial Cells

2009 ◽  
Vol 284 (22) ◽  
pp. 14760-14768 ◽  
Author(s):  
Sanjeev Kumar ◽  
Sawa Kostin ◽  
Jan-Paul Flacke ◽  
H. Peter Reusch ◽  
Yury Ladilov
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Soluble Adenylyl Cyclase ◽  
Coronary Endothelial Cells
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