Bicarbonate‐sensing soluble adenylyl cyclase is present in the cell cytoplasm and nucleus of multiple shark tissues

Abstract

The enzyme soluble adenylyl cyclase (sAC) is directly stimulated by bicarbonate (HCO3 −) to produce the signaling molecule cyclic adenosine monophosphate (cAMP). Because sAC and sAC‐related enzymes are found throughout phyla from cyanobacteria to mammals and they regulate cell physiology in response to internal and external changes in pH, CO2, and HCO3 −, sAC is deemed an evolutionarily conserved acid‐base sensor. Previously, sAC has been reported in dogfish shark and round ray gill cells, where they sense and counteract blood alkalosis by regulating the activity of V‐type H+‐ ATPase. Here, we report the presence of sAC protein in gill, rectal gland, cornea, intestine, white muscle, and heart of leopard shark Triakis semifasciata. Co‐expression of sAC with transmembrane adenylyl cyclases supports the presence of cAMP signaling microdomains. Furthermore, immunohistochemistry on tissue sections, and western blots and cAMP‐activity assays on nucleus‐enriched fractions demonstrate the presence of sAC protein in and around nuclei. These results suggest that sAC modulates multiple physiological processes in shark cells, including nuclear functions.

Differential effects of bicarbonate on severe hypoxia- and hypercapnia-induced cardiac malfunctions in diverse fish species

“…For example, mammalian sAC plays roles in the apoptosis of coronary endothelial cells and cardiomyocytes (Chen et al 2011) and in modulating cardiac hypertrophic responses induced βadrenergic and pressure overloads (Schirmer et al 2018). sAC protein is also abundantly present in the hearts of other elasmobranch (Roa and Tresguerres 2017) and ray-finned fishes (Salmerón et al in press). Very recently, HCO3 --mediated and sAC-mediated regulation of rat basal cardiac contractility was revealed based on the inhibitory effects of KH7 by analyzing sarcomere shortening in isolated cardiomyocytes combined with intracellular Ca 2+ and pH measurements (Espejo et al 2020).…”

“…Furthermore, this recovery of heart rate during severe hypoxia with elevated [HCO3 -] conditions was blocked by the small molecule KH7, a specific sAC inhibitor (Tresguerres et al 2010;Bitterman 2013). Although sAC also is present in the hearts of the leopard shark (Triakis semifasciata) (Roa and Tresguerres 2017) and rainbow trout (Salmerón et al in press), its putative role in modulating heart rate and perhaps force development in fish species other than in hypoxic hagfish hearts has not been investigated.…”

Identification of a molecular pH sensor in coral

“…The specific pHi regulatory proteins under pdsAC control are unknown; however, likely candidates include Na þ /H þ -exchangers, V-H þ -ATPases and Na þ /K þ -ATPases. Evidence for the presence of all of these proteins has been reported in anthozoans [9,24,36], and their activities are regulated by sAC in cells from vertebrate animals [33,[37][38][39][40].…”

Evolutionary links between intra‐ and extracellular acid–base regulation in fish and other aquatic animals

“…However, given that corals are phylogenetically deeply rooted metazoans, the role of sAC in pHi regulation most likely extends to most other animal Phyla. In addition, the presence of sAC in the nucleus of mammalian (Zippin et al, 2004) and shark (Roa & Tresguerres, 2017) cells suggests a conserved role in regulating gene expression in response to changing acid-base conditions (Fig. 3).…”