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PMID: 16902751 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Compartmentalized cAMP/PKA signalling regulates cardiac excitation-contraction coupling.

Journal of muscle research and cell motility ·Vol. 27 ·No. 5-7 ·2006-00-00 ·Pages 399-403

Lissandron V, Zaccolo M

Abstract

The sympathetic control over excitation-contraction coupling (ECC) is mediated by the cAMP/PKA signalling pathway. However, in the myocyte, the same signalling pathway is responsible for triggering a plethora of diverse intracellular functions the control of which must be independent of the regulation of ECC. Here we discuss what are the molecular mechanisms leading to selective modulation of ECC in cardiac myocytes with a particular focus on the role of spatial confinement of PKA subsets and the compartmentalization of cAMP.

MeSH Terms
Adaptor Proteins, Signal Transducing/physiology Animals Cell Compartmentation Cyclic AMP/metabolism Heart/physiology Humans Muscle Cells/metabolism Myocardial Contraction Protein Kinases/metabolism Signal Transduction
Chemicals
Adaptor Proteins, Signal Transducing Cyclic AMP Protein Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lissandron Valentina
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35100, Padova, Italy.
Zaccolo Manuela
References (48)
48 references, click to expand
  1. Ca channels in cardiac myocytes: structure and function in Ca influx and intracellular Ca release.
    Cardiovasc Res. 1999 May;42(2):339-60 PMID: 10533572
  2. Phosphorylation of C-protein, troponin I and phospholamban in isolated rabbit hearts.
    Biochem J. 1988 Feb 1;249(3):709-14 PMID: 2895634
  3. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts.
    Cell. 2000 May 12;101(4):365-76 PMID: 10830164
  4. A genetically encoded, fluorescent indicator for cyclic AMP in living cells.
    Nat Cell Biol. 2000 Jan;2(1):25-9 PMID: 10620803
  5. Phosphorylation of both serine residues in cardiac troponin I is required to decrease the Ca2+ affinity of cardiac troponin C.
    J Biol Chem. 1995 Dec 22;270(51):30773-80 PMID: 8530519
  6. Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases.
    Circ Res. 2004 Jul 9;95(1):67-75 PMID: 15178638
  7. Voltage-dependent potentiation of L-type Ca2+ channels in skeletal muscle cells requires anchored cAMP-dependent protein kinase.
    Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11492-6 PMID: 7972090
  8. Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif.
    J Biol Chem. 1991 Aug 5;266(22):14188-92 PMID: 1860836
  9. Contributions of protein kinase A anchoring proteins to compartmentation of cAMP signaling in the heart.
    Mol Pharmacol. 2002 Aug;62(2):193-9 PMID: 12130668
  10. Spatially resolved dynamics of cAMP and protein kinase A subunits in Aplysia sensory neurons.
    Science. 1993 Apr 9;260(5105):222-6 PMID: 7682336
  11. mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module.
    EMBO J. 2001 Apr 17;20(8):1921-30 PMID: 11296225
  12. AKAP signalling complexes: focal points in space and time.
    Nat Rev Mol Cell Biol. 2004 Dec;5(12):959-70 PMID: 15573134
  13. Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract.
    FEBS Lett. 2005 Jun 13;579(15):3264-70 PMID: 15943971
  14. Analysis of a novel A-kinase anchoring protein 100, (AKAP 100).
    Biochem Soc Trans. 1995 May;23(2):268S PMID: 7672294
  15. Compartmentation of cyclic nucleotide signaling in the heart: the role of A-kinase anchoring proteins.
    Circ Res. 2006 Apr 28;98(8):993-1001 PMID: 16645149
  16. PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization.
    Biochem J. 2003 Feb 15;370(Pt 1):1-18 PMID: 12444918
  17. Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein.
    Curr Biol. 1997 Jan 1;7(1):52-62 PMID: 9000000
  18. The fourth dimension in cellular signaling.
    Science. 2001 Sep 21;293(5538):2204-5 PMID: 11569497
  19. mAKAP and the ryanodine receptor are part of a multi-component signaling complex on the cardiomyocyte nuclear envelope.
    J Cell Sci. 2001 Sep;114(Pt 17):3167-76 PMID: 11590243
  20. Localized effects of cAMP mediated by distinct routes of protein kinase A.
    Physiol Rev. 2004 Jan;84(1):137-67 PMID: 14715913
  21. Selective activation of particulate cAMP-dependent protein kinase by isoproterenol and prostaglandin E1.
    J Biol Chem. 1980 Jun 10;255(11):5113-9 PMID: 6154700
  22. Long PDE4 cAMP specific phosphodiesterases are activated by protein kinase A-mediated phosphorylation of a single serine residue in Upstream Conserved Region 1 (UCR1).
    Br J Pharmacol. 2002 Jun;136(3):421-33 PMID: 12023945
  23. AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation.
    J Biol Chem. 2001 Nov 23;276(47):44247-57 PMID: 11546812
  24. Compartmentalized phosphodiesterase-2 activity blunts beta-adrenergic cardiac inotropy via an NO/cGMP-dependent pathway.
    Circ Res. 2006 Feb 3;98(2):226-34 PMID: 16357307
  25. cAMP compartmentation is responsible for a local activation of cardiac Ca2+ channels by beta-adrenergic agonists.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):295-9 PMID: 8552625
  26. Sodium/calcium exchanger (NCX1) macromolecular complex.
    J Biol Chem. 2003 Aug 1;278(31):28849-55 PMID: 12754202
  27. Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2).
    Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1627-32 PMID: 12571360
  28. Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes.
    Science. 2002 Mar 1;295(5560):1711-5 PMID: 11872839
  29. Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers.
    J Cell Biol. 2001 May 14;153(4):699-708 PMID: 11352932
  30. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias.
    Cell. 2005 Oct 7;123(1):25-35 PMID: 16213210
  31. Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction?
    EMBO J. 1995 May 1;14(9):1952-60 PMID: 7744002
  32. Phosphorylation of the A-kinase-anchoring protein Yotiao contributes to protein kinase A regulation of a heart potassium channel.
    J Biol Chem. 2005 Sep 9;280(36):31347-52 PMID: 16002409
  33. Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel.
    Science. 2002 Jan 18;295(5554):496-9 PMID: 11799244
  34. Beta-adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13093-8 PMID: 14569017
  35. Developmental changes in beta2-adrenergic receptor signaling in ventricular myocytes: the role of Gi proteins and caveolae microdomains.
    Mol Pharmacol. 2003 Jun;63(6):1338-48 PMID: 12761344
  36. Regulation and role of adenylyl cyclase isoforms.
    Annu Rev Pharmacol Toxicol. 2001;41:145-74 PMID: 11264454
  37. Ezrin is a cyclic AMP-dependent protein kinase anchoring protein.
    EMBO J. 1997 Jan 2;16(1):35-43 PMID: 9009265
  38. Beta-adrenergic receptor stimulation increases unloaded shortening velocity of skinned single ventricular myocytes from rats.
    Circ Res. 1994 Mar;74(3):542-9 PMID: 8118962
  39. Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase. Involvement of serine 54 in the enzyme activation.
    J Biol Chem. 1996 Jul 12;271(28):16526-34 PMID: 8663227
  40. Dual site phospholamban phosphorylation and its physiological relevance in the heart.
    Trends Cardiovasc Med. 2002 Feb;12(2):51-6 PMID: 11852250
  41. Primary structure and function of an A kinase anchoring protein associated with calcium channels.
    Neuron. 1998 May;20(5):1017-26 PMID: 9620705
  42. Organization of G proteins and adenylyl cyclase at the plasma membrane.
    Mol Biol Cell. 1997 Dec;8(12):2365-78 PMID: 9398661
  43. Phenylephrine induces activation of CREB in adult rat cardiac myocytes through MSK1 and PKA signaling pathways.
    J Mol Cell Cardiol. 2004 Nov;37(5):1001-11 PMID: 15522277
  44. Cyclic nucleotide-gated channels colocalize with adenylyl cyclase in regions of restricted cAMP diffusion.
    J Gen Physiol. 2000 Aug;116(2):147-61 PMID: 10919863
  45. Functional difference between SERCA2a and SERCA2b Ca2+ pumps and their modulation by phospholamban.
    Biochem J. 1992 Sep 1;286 ( Pt 2):591-5 PMID: 1326945
  46. beta2-adrenergic cAMP signaling is uncoupled from phosphorylation of cytoplasmic proteins in canine heart.
    Circulation. 1999 May 11;99(18):2458-65 PMID: 10318670
  47. Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes.
    Circ Res. 2001 Aug 31;89(5):445-52 PMID: 11532906
  48. Real-time monitoring of the PDE2 activity of live cells: hormone-stimulated cAMP hydrolysis is faster than hormone-stimulated cAMP synthesis.
    J Biol Chem. 2005 Jan 21;280(3):1716-9 PMID: 15557342
Article Info
Journal
Journal of muscle research and cell motility
Abbr.
J Muscle Res Cell Motil
ISSN
0142-4319
DOI
10.1007/s10974-006-9077-2
Published
2006-00-00
Epub
2006-00-11
Pages
399-403
Language
English
Region
Netherlands
NLM ID
8006298
Subset
IM
Grants
Telethon · TCR05005 · Italy
External Links
PubMed source DOI: 10.1007/s10974-006-9077-2 View journal details
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