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Soluble Adenylyl Cyclase (soluble + adenylyl_cyclase)

Distribution by Scientific Domains

Life Sciences	75%

Selected Abstracts

Autoinhibitory regulation of soluble adenylyl cyclase

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2006
James A. Chaloupka
Abstract Soluble adenylyl cyclase is an evolutionarily conserved bicarbonate sensor that plays a crucial role in cAMP dependent processes that occur during mammalian fertilization. sAC protein is expressed at the highest levels in male germ cells, and is found to occur as one of two known isoforms: a truncated protein (sACt) that consists almost exclusively of the two conserved catalytic domains (C1 and C2), and a full-length form (sACfl) that contains an additional noncatalytic C-terminal region. Several studies suggested sACt was more active than sACfl. We now demonstrate that the specific activity of sACt is at least 10-fold higher than the specific activity of sACfl. Using deletion analysis and a novel genetic screen to identify activating mutations, we uncovered an autoinhibitory region just C-terminal to the C2 domain. Kinetic analysis of purified recombinant sAC revealed this autoinhibitory domain functions to lower the enzyme's Vmax without altering its affinity for substrate or regulation by any of the known modulators of sAC activity. Our results identify an additional regulatory mechanism specific to the sACfl isoform. Mol. Reprod. Dev. © 2005 Wiley-Liss, Inc. [source]

"Soluble" adenylyl cyclase-generated cyclic adenosine monophosphate promotes fast migration in PC12 cells

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2008
Jennifer J. Young
Abstract In a model for neuronal movement, PC12 cells undergo fast migration in response to nerve growth factor (NGF) and phorbol ester (PMA). We previously showed that NGF increases intracellular cAMP via activation of soluble adenylyl cyclase (sAC). In this report, we demonstrate that sAC activation is an essential component of NGF- + PMA-induced fast migration in PC12 cells. Interestingly, PMA also raises intracellular cAMP but does so by stimulating transmembrane adenylyl cyclases (tmAC); however, this tmAC-generated cAMP does not contribute to fast migration. Therefore, cells must possess independent pools of cAMP capable of modulating distinct functions. © 2007 Wiley-Liss, Inc. [source]

Alcohol Stimulates Ciliary Motility of Isolated Airway Axonemes Through a Nitric Oxide, Cyclase, and Cyclic Nucleotide-Dependent Kinase Mechanism

ALCOHOLISM, Issue 4 2009
Joseph H. Sisson
Background:, Lung mucociliary clearance provides the first line of defense from lung infections and is impaired in individuals who consume heavy amounts of alcohol. Previous studies have demonstrated that this alcohol-induced ciliary dysfunction occurs through impairment of nitric oxide (NO) and cyclic nucleotide-dependent kinase-signaling pathways in lung airway ciliated epithelial cells. Recent studies have established that all key elements of this alcohol-driven signaling pathway co-localize to the apical surface of the ciliated cells with the basal bodies. These findings led us to hypothesize that alcohol activates the cilia stimulation pathway at the organelle level. To test this hypothesis we performed experiments exposing isolated demembranated cilia (isolated axonemes) to alcohol and studied the effect of alcohol-stimulated ciliary motility on the pathways involved with isolated axoneme activation. Methods:, Isolated demembranated cilia were prepared from bovine trachea and activated with adenosine triphosphate. Ciliary beat frequency, NO production, adenylyl and guanylyl cyclase activities, cAMP- and cGMP-dependent kinase activities were measured following exposure to biologically relevant concentrations of alcohol. Results:, Alcohol rapidly stimulated axoneme beating 40% above baseline at very low concentrations of alcohol (1 to 10 mM). This activation was specific to ethanol, required the synthesis of NO, the activation of soluble adenylyl cyclase (sAC), and the activation of both cAMP- and cGMP-dependent kinases (PKA and PKG), all of which were present in the isolated organelle preparation. Conclusions:, Alcohol rapidly and sequentially activates the eNOS,NO,GC,cGMP,PKG and sAC,cAMP, PKA dual signaling pathways in isolated airway axonemes. These findings indicate a direct effect of alcohol on airway cilia organelle function and fully recapitulate the alcohol-driven activation of cilia known to exist in vivo and in intact lung ciliated cells in vitro following brief moderate alcohol exposure. Furthermore, these findings indicate that airway cilia are exquisitely sensitive to the effects of alcohol and substantiate a key role for alcohol in the alterations of mucociliary clearance associated with even low levels of alcohol intake. We speculate that this same axoneme-based alcohol activation pathway is down regulated following long-term high alcohol exposure and that the isolated axoneme preparation provides an excellent model for studying the mechanism of alcohol-mediated cilia dysfunction. [source]