TY - JOUR
T1 - Metavinculin modulates force transduction in cell adhesion sites
AU - Kanoldt, Verena
AU - Kluger, Carleen
AU - Barz, Christiane
AU - Schweizer, Anna Lena
AU - Ramanujam, Deepak
AU - Windgasse, Lukas
AU - Engelhardt, Stefan
AU - Chrostek-Grashoff, Anna
AU - Grashoff, Carsten
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097667036&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-20125-z
DO - 10.1038/s41467-020-20125-z
M3 - Article
C2 - 33335089
AN - SCOPUS:85097667036
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6403
ER -