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Deconstructing sarcomeric structure-function relations in titin-BioID knock-in mice

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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: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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