Identification of an actin binding surface on vinculin that mediates mechanical cell and focal adhesion properties

Peter M. Thompson, Caitlin E. Tolbert, Kai Shen, Pradeep Kota, Sean M. Palmer, Karen M. Plevock, Albina Orlova, Vitold E. Galkin, Keith Burridge, Edward H. Egelman, Nikolay V. Dokholyan, Richard Superfine, Sharon L. Campbell

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Summary Vinculin, a cytoskeletal scaffold protein essential for embryogenesis and cardiovascular function, localizes to focal adhesions and adherens junctions, connecting cell surface receptors to the actin cytoskeleton. While vinculin interacts with many adhesion proteins, its interaction with filamentous actin regulates cell morphology, motility, and mechanotransduction. Disruption of this interaction lowers cell traction forces and enhances actin flow rates. Although a model for the vinculin:actin complex exists, we recently identified actin-binding deficient mutants of vinculin outside sites predicted to bind actin and developed an alternative model to better define this actin-binding surface, using negative-stain electron microscopy (EM), discrete molecular dynamics, and mutagenesis. Actin-binding deficient vinculin variants expressed in vinculin knockout fibroblasts fail to rescue cell-spreading defects and reduce cellular response to external force. These findings highlight the importance of this actin-binding surface and provide the molecular basis for elucidating additional roles of this interaction, including actin-induced conformational changes that promote actin bundling.

Original languageEnglish (US)
Pages (from-to)697-706
Number of pages10
JournalStructure
Volume22
Issue number5
DOIs
StatePublished - May 6 2014

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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    Thompson, P. M., Tolbert, C. E., Shen, K., Kota, P., Palmer, S. M., Plevock, K. M., Orlova, A., Galkin, V. E., Burridge, K., Egelman, E. H., Dokholyan, N. V., Superfine, R., & Campbell, S. L. (2014). Identification of an actin binding surface on vinculin that mediates mechanical cell and focal adhesion properties. Structure, 22(5), 697-706. https://doi.org/10.1016/j.str.2014.03.002