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Projekt
The functional role of the Z-disc in mechanotransduction and in myofibrillogenesis
Antragsteller
Privatdozent Dr. Robert Stehle
Fachliche Zuordnung
Biophysik
Förderung
Förderung von 2010 bis 2014
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 148688621
Z-discs are the focal points of myofibrillogenesis and provide the anchoring network for the sarcomeric filaments. The structural differentiation of the Z-disc during sarcomerogenesis and the structural complexity of matured Z-discs are reasonably well understood. However, little information exists about the mechanical properties of the Z-disc. We have established techniques to measure passive and Ca2+-activated force, force kinetics and sarcomere dynamics in subcellular myofibrils isolated from mammalian cardiac and skeletal muscle, and for the first time, from skeletal muscle of zebrafish larvae that can be easily manipulated by injection of morpholino modified antisense oligonucleotides. We will 1) elucidate the putative dynamic function of the Z-disc during mechanotransduction, 2) characterize the mechanical anchorage of titin and thin filaments in the Z-disc, and dissect the relative importance of α- actinin, telethonin (T-cap), and capZ to filament and sarcomere stability under mechanical stress during muscle relaxation and contraction, and 3) determine the temporal development of mechanical functions during sarcomerogenesis and their relation to structural maturation of the Z-disc. In collaboration with P4 and P7, the altered mechanical parameters will be correlated with the alterations in the Z-disc proteome and ultrastructure.
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