scholarly journals Identification of FDA-Approved Small Molecules Capable of Disrupting the Calmodulin–Adenylyl Cyclase 8 Interaction through Direct Binding to Calmodulin

2017 ◽  
Vol 9 (2) ◽  
pp. 346-357 ◽  
Author(s):  
Michael P. Hayes ◽  
Monica Soto-Velasquez ◽  
C. Andrew Fowler ◽  
Val J. Watts ◽  
David L. Roman
Keyword(s):  
Small Molecules ◽  
Adenylyl Cyclase ◽  
Direct Binding ◽  
Adenylyl Cyclase 8

scholarly journals Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells

Diabetologia ◽  
2014 ◽  
Vol 58 (2) ◽  
pp. 324-333 ◽  
Author(s):  
Haiqiang Dou ◽  
Changhe Wang ◽  
Xi Wu ◽  
Lijun Yao ◽  
Xiaoyu Zhang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Adenylyl Cyclase ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Calcium Influx ◽  
Adenylyl Cyclase 8

scholarly journals Cyclic AMP Levels, Adenylyl Cyclase Activity, and Their Stimulation by Serotonin Quantif ied in Intact Neurons

1997 ◽  
Vol 110 (3) ◽  
pp. 243-255 ◽  
Author(s):  
Leland C. Sudlow ◽  
Rhanor Gillette
Keyword(s):  
Adenylyl Cyclase ◽  
Dissociation Constants ◽  
Fold Increase ◽  
Nucleotide Metabolism ◽  
Cyclase Activity ◽  
Applied Theory ◽  
Intracellular Camp ◽  
Adenylyl Cyclase Activity ◽  
Direct Binding ◽  
The Many

In molluscan central neurons that express cAMP-gated Na+ current (INa,cAMP), estimates of the cAMP binding affinity of the channels have suggested that effective native intracellular cAMP concentrations should be much higher than characteristic of most cells. Using neurons of the marine opisthobranch snail Pleurobranchaea californica, we applied theory and conventional voltage clamp techniques to use INa,cAMP to report basal levels of endogenous cAMP and adenylyl cyclase, and their stimulation by serotonin. Measurements were calibrated to iontophoretic cAMP injection currents to enable expression of the data in molar terms. In 30 neurons, serotonin stimulated on average a 23-fold increase in submembrane [cAMP], effected largely by an 18-fold increase in adenylyl cyclase activity. Serotonin stimulation of adenylyl cyclase and [cAMP] was inversely proportional to cells' resting adenylyl cyclase activity. Average cAMP concentration at the membrane rose from 3.6 to 27.6 μM, levels consistent with the expected cAMP dissociation constants of the INa,cAMP channels. These measures confirm the functional character of INa,cAMP in the context of high levels of native cAMP. Methods similar to those employed here might be used to establish critical characters of cyclic nucleotide metabolism in the many cells of invertebrates and vertebrates that are being found to express ion currents gated by direct binding of cyclic nucleotides.

Implication of adenylyl cyclase 8 in pathological smooth muscle cell migration occurring in rat and human vascular remodelling

2010 ◽  
Vol 221 (3) ◽  
pp. 331-342 ◽  
Author(s):  
Marie Gueguen ◽  
Zela Keuylian ◽  
Véronique Mateo ◽  
Nathalie Mougenot ◽  
Anne-Marie Lompré ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cell ◽  
Adenylyl Cyclase ◽  
Muscle Cell ◽  
Vascular Remodelling ◽  
Smooth Muscle Cell Migration ◽  
Adenylyl Cyclase 8

Accounting for ligand-bound metal ions in docking small molecules on adenylyl cyclase toxins

2007 ◽  
Vol 67 (3) ◽  
pp. 593-605 ◽  
Author(s):  
Deliang Chen ◽  
Gerd Menche ◽  
Trevor D. Power ◽  
Laurie Sower ◽  
Johnny W. Peterson ◽  
...  
Keyword(s):  
Metal Ions ◽  
Small Molecules ◽  
Adenylyl Cyclase

scholarly journals GABA induces the differentiation of small into large cholangiocytes by activation of Ca2+/CaMK I-dependent adenylyl cyclase 8

Hepatology ◽  
2013 ◽  
Vol 58 (1) ◽  
pp. 251-263 ◽  
Author(s):  
Romina Mancinelli ◽  
Antonio Franchitto ◽  
Shannon Glaser ◽  
Fanyin Meng ◽  
Paolo Onori ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Adenylyl Cyclase 8

scholarly journals Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry

2009 ◽  
Vol 296 (3) ◽  
pp. C607-C619 ◽  
Author(s):  
Mario Pagano ◽  
Michael A. Clynes ◽  
Nanako Masada ◽  
Antonio Ciruela ◽  
Laura-Jo Ayling ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Lipid Rafts ◽  
Leucine Zipper ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Adenylyl Cyclases ◽  
Leucine Zipper Motif ◽  
Capacitative Calcium Entry ◽  
Lipid Raft Microdomains ◽  
Adenylyl Cyclase 8

Adenylyl cyclases (ACs) are a family of critically important signaling molecules that are regulated by multiple pathways. Adenylyl cyclase 8 (AC8) is a Ca2+ stimulated isoform that displays a selective regulation by capacitative Ca2+ entry (CCE), the process whereby the entry of Ca2+ into cells is triggered by the emptying of intracellular stores. This selectivity was believed to be achieved through the localization of AC8 in lipid raft microdomains, along with components of the CCE apparatus. In the present study, we show that an intact leucine zipper motif is required for the efficient N-linked glycosylation of AC8, and that this N-linked glycosylation is important to target AC8 into lipid rafts. Disruption of the leucine zipper by site-directed mutagenesis results in the elimination of N-glycosylated forms and their exclusion from lipid rafts. Mutants of AC8 that cannot be N-glycosylated are not demonstrably associated with rafts, although they can still be regulated by CCE; however, raft integrity is required for the regulation of these mutants. These findings suggest that raft localized proteins in addition to AC8 are needed to mediate its regulation by CCE.

Sign in / Sign up

Export Citation Format

Share Document