Analyzing filamin C homeostasis

蛋白质稳态依赖于蛋白质合成和降解的微调平衡。我们最近发现了一种分子伴侣辅助降解途径，该途径在收缩肌肉中不断运作，将受损的细丝蛋白C（FLNC）导向自噬处理。这种降解途径对于苍蝇、小鼠和人的肌肉维持至关重要。在这里，将阐明伴侣机制在该降解途径上识别和动员FLNC的分子基础。此外，将研究FLNC的折叠和组装，因为连续的处置需要通过连续掺入新合成的FLNC来补偿，以保持Zdisc的完整性。因此，该项目将提供新的见解FLNC和Z-光盘稳态。

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.