Established and potential physiological roles of bicarbonate-sensing soluble adenylyl cyclase (sAC) in aquatic animals

Abstract

Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs). Mammalian sAC is distributed throughout the cytoplasm and it may be present in the nucleus and inside mitochondria. sAC activity is directly stimulated by HCO 3 -, and sAC has been confirmed to be a HCO 3 -sensor in a variety of mammalian cell types. In addition, sAC can functionally associate with carbonic anhydrases to act as a de facto sensor of pH and CO 2 . The two catalytic domains of sAC are related to HCO 3 --regulated adenylyl cyclases from cyanobacteria, suggesting the cAMP pathway is an evolutionarily conserved mechanism for sensing CO 2 levels and/or acid/base conditions. Reports of sAC in aquatic animals are still limited but are rapidly accumulating. In shark gills, sAC senses blood alkalosis and triggers compensatory H + absorption. In the intestine of bony fishes, sAC modulates NaCl and water absorption. And in sea urchin sperm, sAC may participate in the initiation of flagellar movement and in the acrosome reaction. Bioinformatics and RT-PCR results reveal that sAC orthologs are present in most animal phyla. This review summarizes the current knowledge on the physiological roles of sAC in aquatic animals and suggests additional functions in which sAC may be involved.KEY WORDS: V-ATPase, Acid/base, cAMP, Carbonic anhydrase, pH sensing, Proton pump IntroductionCyclic adenosine monophosphate (cAMP) is the signaling molecule of one of the most versatile and evolutionarily conserved signaling pathways. cAMP is produced by adenylyl cyclase enzymes that use ATP as substrate. There are six different classes of adenylyl cyclases distributed throughout Bacteria, Archaea and Eukarya; these classes are unrelated in sequence and structure but all produce cAMP as a result of convergent evolution (Linder and Schultz, 2008). All known eukaryotic adenylyl cyclases, including soluble adenylyl cyclase (sAC) and transmembrane adenylyl cyclase (tmAC) from animals, belong to Class III. Discovery of mammalian sACUntil recently, vertebrate animals were believed to have only one type of adenylyl cyclase, a family of hormone and G-proteinregulated tmACs. Mammals have nine tmAC genes (ADCY1-9), which differ in their tissue and developmental expression as well as in some of their regulatory properties (Cooper, 2003;Hanoune and Defer, 2001 (Braun, 1974;Braun, 1975;Braun, 1990;Braun, 1991;Braun and Dods, 1975). This enzyme was termed 'soluble adenylyl cyclase' (sAC) because its activity is preferentially found in the cytosolic fraction, although some activity is also found associated with membranes. Subsequent immunolocalization and biochemical studies found sAC in the cell cytoplasm and in organelles (Zippin et al., 2003;Zippin et al., 2004). The intracellular localization of sAC changed the assumption that cAMP is produced exclusively in the proximity of the cell membrane by tmACs. Pr...

Maturation of spermatozoa from rainbow trout (Oncorhynchus mykiss) sex-reversed females using artificial seminal plasma or glucose–methanol extender

“…The bicarbonate and high pH elevate cAMP levels in spermatozoa [6,13]. Cyclic adenosine monophosphate is likely produced by soluble adenylyl cyclase [14]. The cAMP-dependent phosphorylation of proteins including protein kinase PKA-C is essential for the initiation of sperm motility in salmonid fishes [15].…”

Novel and potential physiological roles of vacuolar-type H+-ATPase in marine organisms

“…blood A/B regulation (Heisler, 1988), they only have two A/B regulatory cell types, they do not secrete NaCl for osmoregulation (for which elasmobranchs use the rectal gland; see Glossary), and elasmobranch gills routinely deal with massive A/B fluctuations as a result of feeding, exercise and environmental conditions (reviewed in Tresguerres et al, 2014). By contrast, mammals use both lungs and kidneys (reviewed in Boron and Boulpaep, 2012), and their renal cells have multiple A/B regulatory cell types, which are difficult to isolate and cannot withstand large A/B fluctuations in vitro (Breton and Brown, 1998;Gong et al, 2010).…”

Introducing a novel mechanism to control heart rate in the ancestral pacific hagfish

“…Importantly, sAC differs from tmAC by being activated by bicarbonate ions (HCO 3 − ) rather than catecholamines (Buck et al, 1999;Chen et al, 2000;Tresguerres et al, 2010bTresguerres et al, , 2011. Although hagfish sAC has not yet been cloned, sAC genes are present in cartilaginous and bony fishes (Tresguerres et al, 2010b;reviewed in Tresguerres et al, 2014;Tresguerres, 2014), as well as in a variety of invertebrate animals including Trichoiplax, sponges, cnidarians, molluscs, echinoderms, insects and cephalochordates (Barott et al, 2013;Tresguerres, 2014;Tresguerres et al, 2010bTresguerres et al, , 2014. Furthermore, a hallmark of sAC enzymatic activity is HCO 3 − -stimulated cAMP production, which is sensitive to the small inhibitor molecule KH7 (Hess et al, 2005;Tresguerres et al, 2010bTresguerres et al, , 2011.…”