The sarcomeric Z-disc: a nodal point in signalling and disease.
The perception of the Z-disc in striated muscle has undergone significant changes in the past decade. Traditionally, the Z-disc has been viewed as a passive constituent of the sarcomere, which is important only for the cross-linking of thin filaments and transmission of force generated by the myofilaments. The recent discovery of multiple novel molecular components, however, has shed light on an emerging role for the Z-disc in signal transduction in both cardiac and skeletal muscles. Strikingly, mutations in several Z-disc proteins have been shown to cause cardiomyopathies and/or muscular dystrophies. In addition, the elusive cardiac stretch receptor appears to localize to the Z-disc. Various signalling molecules have been shown to interact with Z-disc proteins, several of which shuttle between the Z-disc and other cellular compartments such as the nucleus, underlining the dynamic nature of Z-disc-dependent signalling. In this review, we provide a systematic view on the currently known Z-disc components and the functional significance of the Z-disc as an interface between biomechanical sensing and signalling in cardiac and skeletal muscle functions and diseases.
Frank
Derk
D
Department of Internal Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Kuhn
Christian
C
Katus
Hugo A
HA
Frey
Norbert
N
D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D012518:Sarcomeres / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D015815:Cell Adhesion Molecules; D009124:Muscle Proteins