Signalling-Pathways Regulating the Dynamic Localization of Z-disc-Associated Proteins

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The last few years have witnessed the identification of an unexpectedly high number of proteins associated with the myofibrillar Z-disc. In addition it became evident that mutations in the genes encoding many Z-disc proteins have been found to cause neuromuscular and/or cardiac disease. However, very little is known about the signalling pathways that regulate specific protein-protein interactions and the dynamic state of the Z-disc. The existing map of protein interactions derived from biochemical work provides an excellent basis for a systematic analysis of dynamic protein localization and interactions by using state-of-the-art microscopy methods. We will therefore apply fluorescence microscopy after photobleaching (FRAP) and bimolecular fluorescence complementation (BiFC) measurements in combination with direct interference of signalling pathways. Insights from this project are of immediate importance for the interpretation of protein interaction data (P2, P3, P4, P10), structure determination, analysis and validation of protein complexes (P5, P6), Z-disc ultrastructure analysis and interpretation (P7) and biophysical characterization of Z-disc protein complexes and sarcomer dynamics (P8, P9).