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

Franziska Rudolph, Claudia Fink, Judith Hüttemeister, Marieluise Kirchner, Michael H. Radke, Jacobo Lopez Carballo, Eva Wagner, Tobias Kohl, Stephan E. Lehnart, Philipp Mertins and Michael Gotthardt ()
Additional contact information
Franziska Rudolph: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Claudia Fink: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Judith Hüttemeister: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Marieluise Kirchner: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Michael H. Radke: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Jacobo Lopez Carballo: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Eva Wagner: University Medical Center Göttingen
Tobias Kohl: University Medical Center Göttingen
Stephan E. Lehnart: University Medical Center Göttingen
Philipp Mertins: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Michael Gotthardt: Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16929-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16929-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16929-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().