Analyzing filamin C homeostasis

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Protein homeostasis depends on a fine tuned balance of protein synthesis and degradation. We recently identified a chaperone-assisted degradation pathway, which constantly operates in contracting muscles to direct damaged filamin C (FLNC) towards autophagic disposal. This degradation pathway is essential for muscle maintenance in flies, mice and men. Here the molecular basis of FLNC recognition and mobilization by the chaperone machinery on this degradation pathway will be elucidated. In addition, the folding and assembly of FLNC will be investigated, because continuous disposal needs to be compensated by continuous incorporation of newly synthesized FLNC in order to preserve Zdisc integrity. The project will thus provide novel insights into FLNC and Z-disc homeostasis.