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Cellular Localisation of Adenylyl Cyclase: A Post-genome Perspective

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Abstract

The intracellular messenger cAMP is essential for vital processes ranging from ovulation to cognition. There are 10 genes for adenylyl cyclase (AC), the biosynthetic enzyme of cAMP. Nine of these encode membrane-bound proteins and one gives rise to soluble AC. The understanding of the biological significance of this molecular diversity is incomplete. Membrane-bound ACs conform to the same structural blueprint but have markedly different regulatory characteristics. AC mRNAs are differentially distributed in the body suggesting non-redundant physiological functions. The subcellular localisation of AC isoforms has not been examined in detail. Here we discuss the current knowledge on the intracellular targeting of AC isoforms, and highlight the technical problems of AC detection, some of which appear to be caused by the poor quality-control of commercially supplied antibodies. The principal message is that intracellular targeting of ACs may be isoform-specific and also dependent on the cellular context of expression.

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References

  1. Antoni FA (2000) Molecular diversity of cyclic AMP signaling. Front Neuroendocrinol 21:103–132

    Article  PubMed  CAS  Google Scholar 

  2. Cooper DM (2003) Regulation and organization of adenylyl cyclases and cAMP. Biochem J 375:517–529

    Article  PubMed  CAS  Google Scholar 

  3. Pastor-Soler N, Beaulieu V, Litvin TN, Da Silva N, Chen Y, Brown D, Buck J, Levin LR, Breton S (2003) Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling. J Biol Chem 278:49523–49529

    Article  PubMed  CAS  Google Scholar 

  4. Wang H, Storm DR (2003) Calmodulin-regulated adenylyl cyclases: cross-talk and plasticity in the central nervous system. Mol Pharmacol 63:463–468

    Article  PubMed  Google Scholar 

  5. Okumura S, Takagi G, Kawabe J, Yang G, Lee MC, Hong C, Liu J, Vatner DE, Sadoshima J, Vatner SF, Ishikawa Y (2003) Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload. Proc Natl Acad Sci USA 100:9986–9990

    Article  PubMed  CAS  Google Scholar 

  6. Storm DR, Hansel C, Hacker B, Parent A, Linden DJ (1998) Impaired cerebellar long-term potentiation in type I adenylyl cyclase mutant mice. Neuron 20:1199–1210

    Article  PubMed  CAS  Google Scholar 

  7. Steinberg S, Brunton L (2001) Compartmentation of G protein-coupled signaling pathways in cardiac myocytes. Annu Rev Pharmacol Toxicol 41:751–773

    Article  PubMed  CAS  Google Scholar 

  8. Baillie G, Scott J, Houslay M (2005) Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract. FEBS Lett 579:3264–3270

    Article  PubMed  CAS  Google Scholar 

  9. Nikolaev VO, Bunemann M, Hein L, Hannawacker A, Lohse MJ (2004) Novel single chain cAMP sensors for receptor-induced signal propagation. J Biol Chem 279:37215–37218

    Article  PubMed  CAS  Google Scholar 

  10. DiPilato LM, Cheng X, Zhang J (2004) Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc Natl Acad Sci USA 101:16513–16518

    Article  PubMed  CAS  Google Scholar 

  11. Mongillo M, McSorley T, Evellin S, Sood A, Lissandron V, Terrin A, Huston E, Hannawacker A, Lohse MJ, Pozzan T, Houslay MD, Zaccolo M (2004) Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases. Circ Res 95:67–75

    Article  PubMed  CAS  Google Scholar 

  12. Liu FC, Wu GC, Hsieh ST, Lai HL, Wang HF, Wang TW, Chern Y (1998) Expression of type VI adenylyl cyclase in the central nervous system: implication for a potential regulator of multiple signals in different neurotransmitter systems. FEBS Lett 436:92–98

    Article  PubMed  CAS  Google Scholar 

  13. Wang H, Pineda VV, Chan GC, Wong ST, Muglia LJ, Storm DR (2003) Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation. J Neurosci 23:9710–9718

    PubMed  CAS  Google Scholar 

  14. Mons N, Harry A, Dubourg P, Premont RT, Iyengar R, Cooper DMF (1995) Immunohistochemical localization of adenylyl cyclase in rat-brain indicates a highly selective concentration at synapses. Proc Natl Acad Sci USA 92:8473–8477

    Article  PubMed  CAS  Google Scholar 

  15. Head BP, Patel HH, Roth DM, Lai NC, Niesman IR, Farquhar MG, Insel PA (2005) G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. J Biol Chem 280:31036–31044

    Article  PubMed  CAS  Google Scholar 

  16. Cheng H, Farquhar MG (1976) Presence of adenylate cyclase activity in Golgi and other fractions from rat liver. II. Cytochemical localization within Golgi and ER membranes. J Cell Biol 70:671–684

    Article  PubMed  CAS  Google Scholar 

  17. Zippin JH, Chen Y, Nahirney P, Kamenetsky M, Wuttke MS, Fischman DA, Levin LR, Buck J (2003) Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct signaling microdomains. FASEB J 17:82–84

    PubMed  CAS  Google Scholar 

  18. Fleming YM, Frame MC, Houslay MD (2004) PDE4-regulated cAMP degradation controls the assembly of integrin-dependent actin adhesion structures and REF52 cell migration. J Cell Sci 117:2377–2388

    Article  PubMed  CAS  Google Scholar 

  19. Zaccolo M, Pozzan T (2003) CAMP and Ca2+ interplay: a matter of oscillation patterns. Trends Neurosci 26:53–55

    Article  PubMed  CAS  Google Scholar 

  20. Dodge KL, Khouangsathiene S, Kapiloff MS, Mouton R, Hill EV, Houslay MD, Langeberg LK, Scott JD (2001) mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO J 20:1921–1930

    Article  PubMed  CAS  Google Scholar 

  21. Schwartz JH (2001) The many dimensions of cAMP signaling. PNAS 98:13482–13484

    Article  PubMed  CAS  Google Scholar 

  22. Nagy G, Reim K, Matti U, Brose N, Binz T, Rettig J, Neher E, Sorensen JB (2004) Regulation of releasable vesicle pool sizes by protein kinase A-dependent phosphorylation of SNAP-25. Neuron 41:417–429

    Article  PubMed  CAS  Google Scholar 

  23. Sakaba T, Neher E (2003) Direct modulation of synaptic vesicle priming by GABA(B) receptor activation at a glutamatergic synapse. Nature 424:775–778

    Article  PubMed  CAS  Google Scholar 

  24. Holz GG (2004) Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell. Diabetes 53:5–13

    Article  PubMed  CAS  Google Scholar 

  25. Tesmer JJ, Sprang SR (1998) The structure, catalytic mechanism and regulation of adenylyl cyclase. Curr Opin Struct Biol 8:713–719

    Article  PubMed  CAS  Google Scholar 

  26. Antoni F, Palkovits M, Makara GB, Linton EA, Lowry PJ, Kiss JZ (1983) Immunoreactive corticotropin-releasing factor in the hypothalamo-infundibular tract. Neuroendocrinology 36:415–423

    Article  PubMed  CAS  Google Scholar 

  27. Antoni FA, Linton EA (1989) Immunocytochemical detection of corticotropin releasing-factor: multiple cross-reactions of a widely used carboxy-terminally directed CRF antiserum (rC70) in rat hypothalamus. Neuroscience 29:167–174

    Article  PubMed  CAS  Google Scholar 

  28. Antoni FA, Sosunov AA, Haunso A, Paterson JM, Simpson J (2003) Short-term plasticity of cyclic adenosine 3′,5′-monophosphate signaling in anterior pituitary corticotrope cells: the role of adenylyl cyclase isotypes. Mol Endocrinol 17:692–703

    Article  PubMed  CAS  Google Scholar 

  29. Antoni FA, Palkovits M, Simpson J, Smith SM, Leitch AL, Rosie R, Fink G, Paterson JM (1998) Ca2+/calcineurin-inhibited adenylyl cyclase highly abundant in forebrain regions important for learning and memory. J Neurosci 18:9650–9661

    PubMed  CAS  Google Scholar 

  30. Tsang VC, Wilkins PP (1991) Optimum dissociating condition for immunoaffinity and preferential isolation of antibodies with high specific activity. J Immunol Methods 138:291–299

    Article  PubMed  CAS  Google Scholar 

  31. Wiegand UK, Duncan RR, Greaves J, Chow RH, Shipston MJ, Apps DK (2003) Red, yellow, green go!–A novel tool for microscopic segregation of secretory vesicle pools according to their age. Biochem Soc Trans 31:851–856

    Article  PubMed  CAS  Google Scholar 

  32. Cazalis M, Dayanithi G, Nordmann JJ (1987) Hormone release from isolated nerve endings of the rat neurohypophysis. J Physiol 390:55–70

    PubMed  CAS  Google Scholar 

  33. Antoni FA, Barnard RJO, Shipston MJ, Smith SM, Simpson J, Paterson JM (1995) Calcineurin feedback inhibition of agonist-evoked cAMP formation. J Biol Chem 270:28055–28061

    Article  PubMed  CAS  Google Scholar 

  34. Antoni FA, Smith SM, Simpson J, Rosie R, Fink G, Paterson JM (1998) Calcium control of adenylyl cyclase – the calcineurin connection. Adv Second Messenger Phosphoprotein Res 32:153–172

    PubMed  CAS  Google Scholar 

  35. Paterson JM, Smith SM, Simpson J, Grace OC, Sosunov AA, Bell J, Antoni FA (2000) Characterisation of human adenylyl cyclase IX reveals inhibition by Ca2+/calcineurin and differential mRNA polyadenylation. J Neurochem 75:1358–1367

    Article  PubMed  CAS  Google Scholar 

  36. Baker LP, Nielsen MD, Impey S, Hacker BM, Poser SW, Chan MYM, Storm DR (1999) Regulation and immunohistochemical localization of ßg-stimulated adenylyl cyclases in mouse hippocampus. J Neurosci 19:180–192

    PubMed  CAS  Google Scholar 

  37. Mons N, Yoshimura M, Ikeda H, Hoffman PL, Tabakoff B (1998) Immunological assessment of the distribution of type VII adenylyl cyclase in brain Brain Res 788:251–261

    Article  PubMed  CAS  Google Scholar 

  38. Antoni FA, Simpson J, Sosunov AA (2000) Calcineurin regulated adenylyl cyclase in the brain. In: Gold B, Fischer G, Herdegen T (eds) Immunophilins in the Brain. FKBP ligands: novel strategies for the treatment of neurodegenerative disorders Prous Science, Barcelona, pp. 233–240

    Google Scholar 

  39. Mons N, Harry A, Dubourg P, Premont RT, Iyengar R, Cooper DMF (1995) Immunohistochemical localization of adenylyl cyclase in rat brain indicates a highly selective concentration at synapses. Proc Natl Acad Sci USA 92:8473–8477

    Article  PubMed  CAS  Google Scholar 

  40. Chou JL, Huang CL, Lai HL, Hung AC, Chien CL, Kao YY, Chern Y (2004) Regulation of type VI adenylyl cyclase by Snapin, a SNAP25-binding protein. J Biol Chem 279:46271–46279

    Article  PubMed  CAS  Google Scholar 

  41. Kumar P, Baker L, Storm D, Bowden D (2001) Expression of type I adenylyl cyclase in intrinsic pathways of the hippocampal formation of the macaque (Macaca nemestrina). Neurosci Lett 299:181–184

    Article  PubMed  CAS  Google Scholar 

  42. Higy M, Junne T, Spiess M (2004) Topogenesis of membrane proteins at the endoplasmic reticulum. Biochemistry (Mosc) 43:12716–12722

    Article  CAS  Google Scholar 

  43. Zaccolo M, Pozzan T (2002) Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes. Science 295:1711–1715

    Article  PubMed  CAS  Google Scholar 

  44. Gao T, Puri TS, Gerhardstein BL, Chien AJ, Green RD, Hosey MM (1997) Identification and subcellular localization of the subunits of L-type calcium channels and adenylyl cyclase in cardiac myocytes. J Biol Chem 272:19401–19407

    Article  PubMed  CAS  Google Scholar 

  45. Böl GF, Gros C, Hulster A, Bosel A, Pfeuffer T (1997) Phorbol ester-induced sensitisation of adenylyl cyclase type II is related to phosphorylation of threonine 1057. Biochem Biophys Res Common 237:251–256

    Article  Google Scholar 

  46. Zimmermann G, Taussig R (1996) Protein kinase C alters the responsiveness of adenylyl cyclases to G protein alpha and beta gamma subunits. J Biol Chem 271:27161–27166

    Article  PubMed  CAS  Google Scholar 

  47. Lustig K, Conklin B, Herzmark P, Taussig R, Bourne H (1993) Type II adenylyl cyclase integrates coincident signals from Gs,Gi, and Gq. J Biol Chem 268:13900–13905

    PubMed  CAS  Google Scholar 

  48. Andrade R (1993) Enhancement of beta-adrenergic responses by Gi linked receptors in rat hippocampus. Neuron 10:83–88

    Article  PubMed  CAS  Google Scholar 

  49. Antoni FA, Makara GB, Sosunov AA, Black J, Dayanithi G, Simpson J (2003) Selective expression and transport of adenylyl cyclase isotypes to axon terminals in the neurohypophysis. Eur J Biochem 270(Suppl 1):32

    Google Scholar 

  50. Mons N, Cooper DM (1994) Adenylyl cyclase mRNA expression does not reflect the predominant Ca2+/calmodulin-stimulated activity in the hypothalamus. J Neuroendocrinol 6:665–671

    Article  PubMed  CAS  Google Scholar 

  51. Wang Y, Sugita S, Sudhof TC (2000) The RIM/NIM family of neuronal C2 domain proteins. Interactions with Rab3 and a new class of Src homology 3 domain proteins. J Biol Chem 275:20033–20044

    Article  PubMed  CAS  Google Scholar 

  52. MacEwan D, Kim G, Milligan G (1996) Agonist regulation of adenylate cyclase activity in neuroblastoma × glioma hybrid NG108–15 cells transfected to co-express adenylate cyclase type II and the beta 2-adrenoceptor. Evidence that adenylate cyclase is the limiting component for receptor-mediated stimulation of adenylate cyclase activity. Biochem J 318(Pt 3):1033–1039

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by MRC U.K., and a vacation scholarship to J.B. from the Neural Plasticity and Learning IDG, University of Edinburgh.

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Authors and Affiliations

  1. Division of Neuroscience, University of Edinburgh, EH8 9JZ, Scotland, UK

    Ferenc A. Antoni, Jamie Black & James Simpson

  2. Membrane Biology Group, University of Edinburgh, Edinburgh, EH8 9XD, Scotland, UK

    Ulrich K. Wiegand

  3. Division of Neuroscience, University of Edinburgh, 1 George Sq Edinburgh , EH8 9JZ, Scotland, UK

    Ferenc A. Antoni

Authors
  1. Ferenc A. Antoni
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  2. Ulrich K. Wiegand
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  3. Jamie Black
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  4. James Simpson
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Correspondence to Ferenc A. Antoni.

Additional information

Invocation: This paper was written to honour one of the founders of chemical neuroanatomy—Professor Miklós Palkovits on his 70th birthday.

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Antoni, F.A., Wiegand, U.K., Black, J. et al. Cellular Localisation of Adenylyl Cyclase: A Post-genome Perspective. Neurochem Res 31, 287–295 (2006). https://doi.org/10.1007/s11064-005-9019-1

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  • DOI: https://doi.org/10.1007/s11064-005-9019-1

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