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  Metavinculin modulates force transduction in cell adhesion sites

Kanoldt, V., Kluger, C., Barz, C., Schweizer, A.-L., Ramanujam, D., Windgasse, L., et al. (2020). Metavinculin modulates force transduction in cell adhesion sites. Nature Communications, 11(1): 6403. doi:10.1038/s41467-020-20125-z.

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 Creators:
Kanoldt, Verena1, Author              
Kluger, Carleen1, Author              
Barz, Christiane1, Author              
Schweizer, Anna-Lena1, Author              
Ramanujam, Deepak2, Author
Windgasse, Lukas2, Author
Engelhardt, Stefan2, Author
Chrostek-Grashoff, Anna1, Author              
Grashoff, Carsten1, Author              
Affiliations:
1Grashoff, Carsten / Molecular Mechanotransduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565150              
2external, ou_persistent22              

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Free keywords: META-VINCULIN; ACTIN ORGANIZATION; STRUCTURAL BASIS; FOCAL ADHESIONS; HUMAN-TISSUES; EXPRESSION; TALIN; GENE; TENSION; BINDINGScience & Technology - Other Topics;
 Abstract: Vinculin is a ubiquitously expressed protein, crucial for the regulation of force transduction in cells. Muscle cells express a vinculin splice-isoform called metavinculin, which has been associated with cardiomyopathies. However, the molecular function of metavinculin has remained unclear and its role for heart muscle disorders undefined. Here, we have employed a set of piconewton-sensitive tension sensors to probe metavinculin mechanics in cells. Our experiments reveal that metavinculin bears higher molecular forces but is less frequently engaged as compared to vinculin, leading to altered force propagation in cell adhesions. In addition, we have generated knockout mice to investigate the consequences of metavinculin loss in vivo. Unexpectedly, these animals display an unaltered tissue response in a cardiac hypertrophy model. Together, the data reveal that the transduction of cell adhesion forces is modulated by expression of metavinculin, yet its role for heart muscle function seems more subtle than previously thought. Muscle cells express an adhesion molecule called metavinculin, which has been associated with cardiomyopathies. Here, the authors employed molecular tension sensors to reveal that metavinculin expression modulates cell adhesion mechanics and they develop a mouse model to demonstrate that the presence of metavinculin is not as critical for heart muscle function as previously thought.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 10
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Project name : Collaborative Research Consortium SFB 863 (INST 95/1209-3, GR3399/4-1) and INST 211/861-1
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Funding organization : German Research Foundation

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 11 (1) Sequence Number: 6403 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723