Molecular conversations with soluble adenylyl cyclase A journey of serendipity

Adenylyl cyclases are enzymes that produce cAMP. In contrast to the more well-known transmembrane adenylyl cyclases, soluble adenylyl cyclase (sAC) is found in the cytoplasm and in intracellular organelles. sAC is also not regulated by G-proteins or activated by forskolin; instead, it is regulated by intracellular bicarbonate, calcium, and ATP concentrations. Recent studies have demonstrated the role of sAC-specific cAMP in various tissue-specific and cell autonomous contexts. Despite these unique known properties and functions, not much is known about how cellular sAC protein levels are regulated or maintained. In this thesis, using the H69 cholangiocyte cell line as our model, we set out to investigate how sAC is regulated at the post-translational level and is involved in cholangiocyte-specific functions and physiology, such as cellular apoptosis and ciliogenesis. The observations presented in this thesis imply that sAC could potentially be therapeutically targeted to restore or maintain cholangiocyte physiology in diseases such as primary biliary cholangitis or polycystic liver disease.