FOR 1352:  Structure, Function and Regulation of the Myofibrillar Z-disc Interactome

• Subject Area: Biology
• Term: from 2010 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 148688621

Traditionally, the myofibrillar Z-disc was considered as a passive and stable structure, which links thin filaments from neighbouring sarcomeres and passively transmits force during contraction. This classic view of the Z-disc has strongly changed upon the discovery of a plethora of new Z-disc proteins and of their pleiotropic functions in development, turnover and signal transduction. The importance of the Z-disc is further emphasised by the finding that mutations in genes encoding several Z-disc proteins cause neuromuscular diseases and/or cardiomyopathies. However, the precise molecular layout of the Z-disc, its dynamics and its specific role in signal transduction are far from being understood.
This Research Unit will, therefore, focus on the following topics: (1) functional characterisation of Z-disc proteins and their regulation in vitro and in vivo; (2) compilation of the Z-disc proteome and its functional subcomplexes; (3) generation of structural information of the Z-disc at molecular, supramolecular and ultrastructural levels; (4) elucidation of biophysical and biomechanical properties of single proteins, selected complexes and individual myofibrils.
This Research Unit offers the unique opportunity to unravel the dynamic organisation, function and regulation of the sarcomeric Z-disc, in both health and disease and will have major impact on current and future research in this area.

• DFG Programme: Research Units
• International Connection: Austria

Projects

• Analyzing filamin C homeostasis (Applicant Höhfeld, Jörg )
• Coordination project (Applicant Fürst, Dieter O. )
• Mechanics of Z-disc Proteins (Applicant Rief, Matthias )
• Role of CEFIP, a Novel Z-disc Protein, in Cardiac Hypertrophy and Cardiomyopathy (Applicant Frey, Norbert )
• Signalling-Pathways Regulating the Dynamic Localization of Z-disc-Associated Proteins (Applicants Fleischmann, Bernd ;  Fürst, Dieter O. )
• Structural Basis of Z-disc Protein/Protein Networks and Functional Implications (Applicant Wilmanns, Ph.D., Matthias )
• Structural investigation of the Z-disc by cryo-electron tomography (Applicant Frangakis, Achilleas )
• Structure and Regulation of the Myofibrillar Z-disc Interactome (Applicant Djinovic-Carugo, Kristina )
• Study of Z-disc protein interaction and signaling networks (Applicant Warscheid, Bettina )
• The functional role of the Z-disc in mechanotransduction and in myofibrillogenesis (Applicant Stehle, Robert )
• Z-disc Titin in Sarcomere Assembly and Mechanotransduction (Applicant Gotthardt, Michael )

• Spokesperson: Professor Dr. Dieter O. Fürst