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

2020 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Deconstructing sarcomeric structure–function relations in titin-BioID knock-in mice​
Rudolph, F.; Fink, C.; Hüttemeister, J.; Kirchner, M.; Radke, M. H.; Lopez Carballo, J. & Wagner, E.  et al.​ (2020) 
Nature Communications11(1).​ DOI: https://doi.org/10.1038/s41467-020-16929-8 

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Authors
Rudolph, Franziska; Fink, Claudia; Hüttemeister, Judith; Kirchner, Marieluise; Radke, Michael H.; Lopez Carballo, Jacobo; Wagner, Eva ; Kohl, Tobias ; Lehnart, Stephan Elmar ; Mertins, Philipp; Gotthardt, Michael
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.
Issue Date
2020
Journal
Nature Communications 
Project
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse 
Working Group
RG Lehnart (Cellular Biophysics and Translational Cardiology Section) 
eISSN
2041-1723
Language
English

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