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Study of Z-disc protein interaction and signaling networks
Antragstellerin
Professorin Dr. Bettina Warscheid
Fachliche Zuordnung
Biochemie
Förderung
Förderung von 2010 bis 2019
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 148688621
Recent discoveries of various new constituents of the myofibrillar Z-disc provided valuable insights into the molecular architecture and function of this vital structure. However, it is reasonable to assume that the composition of the Z-disc proteome, its protein-protein interaction network and the dynamic aspects involved are far from being comprehended. In addition to the identification of new Z-disc proteins, we thus set out to accurately characterize dynamic alterations in myofibrillar proteomes and the Z-disc interactome as well as to investigate distinct intracellular signalling pathways associated with Z-disc function in health and disease. Through application of latest quantitative (phospho)proteomic methodology with high-resolution mass spectrometry (MS) as key technology we will identify both stable and transient protein-protein interactions as well as monitor reversible phosphorylation events in proteins and quantitative changes in the myofibrillar proteome of zebrafish morphants, in which the expression of a given Z-disc protein is downregulated. Our results will (1) complement structural analyses and biochemical studies of individual protein complexes in the Z-disc (P1, P2, P5, and P6); (2) make a significant contribution to the characterization of signalling pathways regulating the dynamic localization of Z-disc proteins (P1); and (3) assist in a better understanding of Z-disc function in sarcomere stability and myofibrillogenesis (P9).
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