Molecular basis and cellular functions of vinculin-actin directional catch bonding

The ability of cells and tissues to respond differentially to mechanical forces applied in distinct directions is mediated by the ability of load-bearing proteins to preferentially maintain physical linkages in certain directions. However, the molecular basis and biological consequences of direction...

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Bibliographic Details
Published in:Nature communications 2023-12, Vol.14 (1), p.8300-8300, Article 8300
Main Authors: Chirasani, Venkat R., Khan, Mohammad Ashhar I., Malavade, Juilee N., Dokholyan, Nikolay V., Hoffman, Brenton D., Campbell, Sharon L.
Format: Article
Language:English
Subjects:
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Actin
Binding
Biochemistry
Biology
Cell adhesion & migration
Cell migration
Cellular structure
Cytoskeleton
Humanities and Social Sciences
Load
Motility
multidisciplinary
Phospholipids
Proteins
Science
Science (multidisciplinary)
Simulation
Vinculin
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Summary:The ability of cells and tissues to respond differentially to mechanical forces applied in distinct directions is mediated by the ability of load-bearing proteins to preferentially maintain physical linkages in certain directions. However, the molecular basis and biological consequences of directional force-sensitive binding remain unclear. Vinculin (Vcn) is a load-bearing linker protein that exhibits directional catch bonding due to interactions between the Vcn tail domain (Vt) and filamentous (F)-actin. We developed a computational approach to predict Vcn residues involved in directional catch bonding and produced a set of associated Vcn variants with unaltered Vt structure, actin binding, or phospholipid interactions. Incorporation of the variants did not affect Vcn activation but reduced Vcn loading and altered exchange dynamics, consistent with the loss of directional catch bonding. Expression of Vcn variants perturbed the coordination of subcellular structures and cell migration, establishing key cellular functions for Vcn directional catch bonding. This study provides insights into the directional catch bonding of the linker protein vinculin by elucidating the molecular basis of mechanical reinforcement as well as unveiling its key role in subcellular organization and cellular processes.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-43779-x