doi: 10.1161/01.RES.0000116143.74830.A9
© 2004 American Heart Association, Inc.
Reviews |
At the Crossroads of Myocardial Signaling
The Role of Z-Discs in Intracellular Signaling and Cardiac Function
From the Department of Biomedical Sciences (W.G.P.), University of Guelph, Guelph, Ontario, Canada; Department of Physiology and Biophysics (R.J.S.), College of Medicine, University of Illinois at Chicago, Chicago, Ill.
Correspondence to R. John Solaro, PhD, Department of Physiology and Biophysics, (M/C 901), College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, Chicago, IL 60612-7342. E-mail SolaroRJ{at}uic.edu
This Review is part of a thematic series on Regulatory Signaling by Thin Filament Modulation, which includes the following articles:
Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins: Physiological and Pathological Implications
Covalent and Noncovalent Modification of Thin Filament Action: The Essential Role of Troponin in Cardiac Muscle Regulation
At the Crossroads of Myocardial Signaling: The Role of Z-Discs in Intracellular Signaling and Cardiac Function
Modulation of Thin Filament Activation by Crossbridges
R. John Solaro Guest Editor
Understanding the molecular interactions among components of cardiac Z-discs and their role in signaling has become pivotal in explaining long- and short-term regulation of cardiac function. In striated muscle, the ends of the thin filaments from opposing sarcomeres overlap and are cross-linked by an elaborate array of proteins to form a highly ordered, yet dynamic network that is the Z-disc. We review here a current picture of the function and structure of the Z-disc of mammalian cardiac myocytes. We emphasize provocative findings that advance new theories about the place of cardiac Z-discs in myocardial intra- and intercellular signaling in myocardial physiology and pathology. Relatively new approaches, especially yeast two-hybrid screens, immunoprecipitation, and pull down assays, as well as immunohistochemical analysis have significantly altered previous views of the protein content of the Z-disc. These studies have generally defined domain structure and binding partners for Z-disc proteins, but the functional significance of the binding network and of the domains in cardiac cell biology remains an unfolding story. Yet, even at the present level of understanding, perceptions of potential functions of the Z-disc proteins are expanding greatly and leading to new and exciting experimental approaches toward mechanistic understanding. The theme of the following discussion of these Z-disc proteins centers on their potential to function not only as a physical anchor for myofilament and cytoskeletal proteins, but also as a pivot for reception, transduction, and transmission of mechanical and biochemical signals.
Key Words: signal transduction • sarcomere • diastolic function • myopathies • hypertrophy
This article has been cited by other articles:
 |
|
 |
|
  P. von Nandelstadh, M. Ismail, C. Gardin, H. Suila, I. Zara, A. Belgrano, G. Valle, O. Carpen, and G. Faulkner A Class III PDZ Binding Motif in the Myotilin and FATZ Families Binds Enigma Family Proteins: a Common Link for Z-Disc Myopathies Mol. Cell. Biol., February 1, 2009; 29(3): 822 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Risebro, R. G. Searles, A. A. D. Melville, E. Ehler, N. Jina, S. Shah, J. Pallas, M. Hubank, M. Dillard, N. L. Harvey, et al. Prox1 maintains muscle structure and growth in the developing heart Development, February 1, 2009; 136(3): 495 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Walker, T.K. Rajendra, L. Saieva, J. L. Fuentes, L. Pellizzoni, and A. G. Matera SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain Hum. Mol. Genet., November 1, 2008; 17(21): 3399 - 3410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Solaro Multiplex Kinase Signaling Modifies Cardiac Function at the Level of Sarcomeric Proteins J. Biol. Chem., October 3, 2008; 283(40): 26829 - 26833. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tagawa, T. Ueyama, T. Ogata, N. Takehara, N. Nakajima, K. Isodono, S. Asada, T. Takahashi, H. Matsubara, and H. Oh MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis Am J Physiol Cell Physiol, August 1, 2008; 295(2): C490 - C498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, C. F. Browning, H. Hallaq, L. Yermalitskaya, J. Esker, M. R. Hall, A. J. Link, A.-J. L. Ham, M. J. McGrath, C. A. Mitchell, et al. Four and a half LIM protein 1: a partner for KCNA5 in human atrium Cardiovasc Res, June 1, 2008; 78(3): 449 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ogata, T. Ueyama, K. Isodono, M. Tagawa, N. Takehara, T. Kawashima, K. Harada, T. Takahashi, T. Shioi, H. Matsubara, et al. MURC, a Muscle-Restricted Coiled-Coil Protein That Modulates the Rho/ROCK Pathway, Induces Cardiac Dysfunction and Conduction Disturbance Mol. Cell. Biol., May 15, 2008; 28(10): 3424 - 3436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Linke Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction Cardiovasc Res, March 1, 2008; 77(4): 637 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Boateng and P. H. Goldspink Assembly and maintenance of the sarcomere night and day Cardiovasc Res, March 1, 2008; 77(4): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Faul, A. Dhume, A. D. Schecter, and P. Mundel Protein Kinase A, Ca2+/Calmodulin-Dependent Kinase II, and Calcineurin Regulate the Intracellular Trafficking of Myopodin between the Z-Disc and the Nucleus of Cardiac Myocytes Mol. Cell. Biol., December 1, 2007; 27(23): 8215 - 8227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Frank, C. Kuhn, M. van Eickels, D. Gehring, C. Hanselmann, S. Lippl, R. Will, H. A. Katus, and N. Frey Calsarcin-1 Protects Against Angiotensin-II Induced Cardiac Hypertrophy Circulation, November 27, 2007; 116(22): 2587 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Karagulova, Y. Yue, A. Moreyra, M. Boutjdir, and I. Korichneva Protective Role of Intracellular Zinc in Myocardial Ischemia/Reperfusion Is Associated with Preservation of Protein Kinase C Isoforms J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 517 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Donker, J. G. Maessen, F. Verheyen, F. C. Ramaekers, R. L. H. M. G. Spatjens, H. Kuijpers, C. Ramakers, P. M. H. Schiffers, M. A. Vos, H. J. G. M. Crijns, et al. Impact of acute and enduring volume overload on mechanotransduction and cytoskeletal integrity of canine left ventricular myocardium Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2324 - H2332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cuello, S. C. Bardswell, R. S. Haworth, X. Yin, S. Lutz, T. Wieland, M. Mayr, J. C. Kentish, and M. Avkiran Protein Kinase D Selectively Targets Cardiac Troponin I and Regulates Myofilament Ca2+ Sensitivity in Ventricular Myocytes Circ. Res., March 30, 2007; 100(6): 864 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Barrientos, D. Frank, K. Kuwahara, S. Bezprozvannaya, G. C. T. Pipes, R. Bassel-Duby, J. A. Richardson, H. A. Katus, E. N. Olson, and N. Frey Two Novel Members of the ABLIM Protein Family, ABLIM-2 and -3, Associate with STARS and Directly Bind F-actin J. Biol. Chem., March 16, 2007; 282(11): 8393 - 8403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Laustsen, S. J. Russell, L. Cui, A. Entingh-Pearsall, M. Holzenberger, R. Liao, and C. R. Kahn Essential Role of Insulin and Insulin-Like Growth Factor 1 Receptor Signaling in Cardiac Development and Function Mol. Cell. Biol., March 1, 2007; 27(5): 1649 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Moza, L. Mologni, R. Trokovic, G. Faulkner, J. Partanen, and O. Carpen Targeted Deletion of the Muscular Dystrophy Gene myotilin Does Not Perturb Muscle Structure or Function in Mice Mol. Cell. Biol., January 1, 2007; 27(1): 244 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hoshijima Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1313 - H1325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Samarel Costameres, focal adhesions, and cardiomyocyte mechanotransduction Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2291 - H2301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Maddatu, S. M. Garvey, D. G. Schroeder, W. Zhang, S.-Y. Kim, A. I. Nicholson, C. J. Davis, and G. A. Cox Dilated cardiomyopathy in the nmd mouse: transgenic rescue and QTLs that improve cardiac function and survival Hum. Mol. Genet., November 1, 2005; 14(21): 3179 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Torsoni, T. M. Marin, L. A. Velloso, and K. G. Franchini RhoA/ROCK signaling is critical to FAK activation by cyclic stretch in cardiac myocytes Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1488 - H1496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Guzzo, M. Salih, E. D. Moore, and B. S. Tuana Molecular properties of cardiac tail-anchored membrane protein SLMAP are consistent with structural role in arrangement of excitation-contraction coupling apparatus Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1810 - H1819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Heineke, H. Ruetten, C. Willenbockel, S. C. Gross, M. Naguib, A. Schaefer, T. Kempf, D. Hilfiker-Kleiner, P. Caroni, T. Kraft, et al. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc PNAS, February 1, 2005; 102(5): 1655 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Schoffstall, A. Kataoka, A. Clark, and P. B. Chase Effects of Rapamycin on Cardiac and Skeletal Muscle Contraction and Crossbridge Cycling J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 12 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Miano, N. Ramanan, M. A. Georger, K. L. de Mesy Bentley, R. L. Emerson, R. O. Balza Jr., Q. Xiao, H. Weiler, D. D. Ginty, and R. P. Misra Restricted inactivation of serum response factor to the cardiovascular system PNAS, December 7, 2004; 101(49): 17132 - 17137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Walker and P. P. de Tombe Titin and the Developing Heart Circ. Res., April 16, 2004; 94(7): 860 - 862. [Full Text] [PDF]
|
|