Metavinculin modulates force transduction in cell adhesion sites.
Verena KanoldtCarleen KlugerChristiane BarzAnna-Lena SchweizerDeepak RamanujamLukas WindgasseStefan EngelhardtAnna Chrostek-GrashoffCarsten GrashoffPublished in: Nature communications (2020)
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.
Keyphrases
- cell adhesion
- induced apoptosis
- cell cycle arrest
- single molecule
- skeletal muscle
- single cell
- heart failure
- endoplasmic reticulum stress
- poor prognosis
- atrial fibrillation
- genome wide
- signaling pathway
- gene expression
- oxidative stress
- cell proliferation
- bone marrow
- cell therapy
- binding protein
- dna methylation
- big data
- living cells
- low cost