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
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