Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Adenylyl Cyclase

  • Carmen W. Dessauer
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_420

Synonyms

Historical Background

Adenylyl cyclases (ACs) and ATP-pyrophosphate lyases comprise a family of enzymes that catalyze the synthesis of cyclic AMP from ATP. Cyclic AMP (cAMP) was identified in 1957 as the first “second messenger,” relaying signals from hormone-bound receptors to protein kinase A (PKA) and other cAMP-sensitive effectors, including cyclic-nucleotide gated channels, cAMP-activated exchange proteins (EPAC), and a subset of phosphodiesterases that degrade cyclic nucleotides. Catalytic activity of AC is regulated in response to activation of G protein-coupled receptors (GPCRs) by a number of hormones and neurotransmitters. Various studies using biochemical and genetic tools have implicated the importance of cAMP in a variety of physiological functions that include but are not limited to oogenesis, embryogenesis larval development, hormone secretion, glycogen breakdown, smooth muscle relaxation, cardiac contraction, olfaction, water...

This is a preview of subscription content, log in to check access.

References

  1. Beavo JA, Brunton LL. Cyclic nucleotide research – still expanding after half a century. Nat Rev Mol Cell Biol. 2002;3:710–8.PubMedCrossRefGoogle Scholar
  2. Beazely MA, Watts VJ. Regulatory properties of adenylate cyclases type 5 and 6: a progress report. Eur J Pharmacol. 2006;535:1–12.PubMedCrossRefGoogle Scholar
  3. Brust TF, Conley JM, Watts VJ. Gα(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later. Eur J Pharmacol. 2015;763:223–32.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Chien C-L, Y-S W, Lai H-L, Chen Y-H, Jiang S-T, Shih C-M, et al. Impaired water reabsorption in mice deficient in the type VI adenylyl cyclase (AC6). FEBS Lett. 2010;584:2883–90.PubMedCrossRefGoogle Scholar
  5. Dessauer CW. Adenylyl cyclase–A-kinase anchoring protein complexes: the next dimension in cAMP signaling. Mol Pharmacol. 2009;76:935–41.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Duan B, Davis R, Sadat EL, Collins J, Sternweis PC, Yuan D, et al. Distinct roles of adenylyl cyclase VII in regulating the immune responses in mice. J Immunol. 2010;185:335–44.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Efendiev R, Dessauer CWA. kinase-anchoring proteins and adenylyl cyclase in cardiovascular physiology and pathology. J Cardiovasc Pharmacol. 2011;58:339–44.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Halls ML, Cooper DM. Regulation by Ca2+-signaling pathways of adenylyl cyclase. Cold Spring harb Perspect Biol. 2011;3:a004143.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Ho D, Yan L, Iwatsubo K, Vatner D, Vatner S. Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5. Heart Fail Rev. 2010;15:495–512.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Iwamoto T, Okumura S, Iwatsubo K, Kawabe J, Ohtsu K, Sakai I, et al. Motor dysfunction in type 5 adenylyl cyclase-null mice. J Biol Chem. 2003;278:16936–40.PubMedCrossRefGoogle Scholar
  11. Iwatsubo K, Okumura S, Ishikawa Y. Drug therapy aimed at adenylyl cyclase to regulate cyclic nucleotide signaling. Endocr Metab Immune Disord Drug Targets. 2006;6:239–47.PubMedCrossRefGoogle Scholar
  12. Levin LR and Buck J. Physiological roles of acid-base sensors. Annu Rev Physiology. 2015;77:347–362.PubMedCrossRefGoogle Scholar
  13. Navedo MF, Nieves-Cintron M, Amberg GC, Yuan C, Votaw VS, Lederer WJ, et al. AKAP150 is required for stuttering persistent Ca2+ sparklets and angiotensin II-induced hypertension. Circ Res. 2008;102:e1–11.PubMedCrossRefGoogle Scholar
  14. Pierre S, Eschenhagen T, Geisslinger G, Scholich K. Capturing adenylyl cyclases as potential drug targets. Nat Rev Drug Discov. 2009;8:321–35.PubMedCrossRefGoogle Scholar
  15. Rieg T, Tang T, Murray F, Schroth J, Insel PA, Fenton RA, et al. Adenylate cyclase 6 determines cAMP formation and aquaporin-2 phosphorylation and trafficking in inner medulla. J Am Soc Nephrol. 2010;21:2059–68.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Sadana R, Dessauer CW. Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies. Neurosignals. 2009;17:5–22.PubMedCrossRefGoogle Scholar
  17. Sinha SC, Sprang SR. Structures, mechanism, regulation and evolution of class III nucleotidyl cyclases. Rev Physiol Biochem Pharmacol. 2006;157:105–40.PubMedCrossRefGoogle Scholar
  18. Tang T, Gao MH, Lai NC, Firth AL, Takahashi T, Guo T, et al. Adenylyl cyclase type 6 deletion decreases left ventricular function via impaired calcium handling. Circulation. 2008;117:61–9.PubMedCrossRefGoogle Scholar
  19. Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gs∝.GTP-γS. Science. 1997;278:1907–16.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Wang H, Ferguson GD, Pineda VV, Cundiff PE, Storm DR. Overexpression of type-1 adenylyl cyclase in mouse forebrain enhances recognition memory and LTP. Nat Neurosci. 2004;7:635–42.PubMedCrossRefGoogle Scholar
  21. Wang H, Pineda VV, Chan GC, Wong ST, Muglia LJ, Storm DR. Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation. J Neurosci. 2003;23:9710–8.PubMedCrossRefGoogle Scholar
  22. Wang Z, Nudelman A, Storm DR. Are pheromones detected through the main olfactory epithelium? Mol Neurobiol. 2007;35:317–23.PubMedCrossRefGoogle Scholar
  23. Willoughby D, Cooper DM. Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains. Physiol Rev. 2007;87:965–1010.PubMedCrossRefGoogle Scholar
  24. Wu ZL, Thomas SA, Villacres EC, Xia Z, Simmons ML, Chavkin C, et al. Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice. Proc Natl Acad Sci USA. 1995;92:220–4.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Yan L, Vatner DE, O'Connor JP, Ivessa A, Ge H, Chen W, et al. Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell. 2007;130:247–58.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Integrative Biology and PharmacologyMcGovern Medical School at the University of Texas Health Science Center at HoustonHoustonUSA