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| Item Type: | Article |
|---|---|
| Title: | Deconstructing sarcomeric structure-function relations in titin-BioID knock-in mice |
| Creators Name: | Rudolph, F. and Fink, C. and Hüttemeister, J. and Kirchner, M. and Radke, M.H. and Lopez Carballo, J. and Wagner, E. and Kohl, T. and Lehnart, S.E. and Mertins, P. and Gotthardt, M. |
| Abstract: | Proximity proteomics has greatly advanced the analysis of native protein complexes and subcellular structures in culture, but has not been amenable to study development and disease in vivo. Here, we have generated a knock-in mouse with the biotin ligase (BioID) inserted at titin's Z-disc region to identify protein networks that connect the sarcomere to signal transduction and metabolism. Our census of the sarcomeric proteome from neonatal to adult heart and quadriceps reveals how perinatal signaling, protein homeostasis and the shift to adult energy metabolism shape the properties of striated muscle cells. Mapping biotinylation sites to sarcomere structures refines our understanding of myofilament dynamics and supports the hypothesis that myosin filaments penetrate Z-discs to dampen contraction. Extending this proof of concept study to BioID fusion proteins generated with Crispr/CAS9 in animal models recapitulating human pathology will facilitate the future analysis of molecular machines and signaling hubs in physiological, pharmacological, and disease context. |
| Keywords: | Animal Models, Biotinylation, Carbon-Nitrogen Ligases, Escherichia Coli Proteins, Gene Knock-In Techniques, Metabolic Networks and Pathways, Myocardium, Newborn Animals, Proof of Concept Study, Protein Interaction Maps, Protein Kinases, Proteome, Proteomics, Proteostasis, Quadriceps Muscle, Repressor Proteins, Sarcomeres, Signal Transduction, Structure-Activity Relationship, Transgenic Mice, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 11 |
| Number: | 1 |
| Page Range: | 3133 |
| Date: | 19 June 2020 |
| Official Publication: | https://doi.org/10.1038/s41467-020-16929-8 |
| PubMed: | View item in PubMed |
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