CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics

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• 作者：Radoslav Jano?tiak (1)
  Jan Brábek (1)
  Vera Auernheimer (2)
  Zuzana Tatárová (1)
  Lena A. Lautscham (2)
  Tuli Dey (2)
  Jakub Gemperle (1)
  Rudolf Merkel (3)
  Wolfgang H. Goldmann (2)
  Ben Fabry (2)
  Daniel R?sel (1)
  
• 关键词：CAS ; Focal adhesions ; Mechanosensing ; Vinculin ; Src ; Traction forces
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：71
• 期：4
• 页码：727-744
• 全文大小：1,165 KB
• 作者单位：Radoslav Jano?tiak (1)
  Jan Brábek (1)
  Vera Auernheimer (2)
  Zuzana Tatárová (1)
  Lena A. Lautscham (2)
  Tuli Dey (2)
  Jakub Gemperle (1)
  Rudolf Merkel (3)
  Wolfgang H. Goldmann (2)
  Ben Fabry (2)
  Daniel R?sel (1)
  
  1. Department of Cell Biology, Faculty of Science, Charles University in Prague, Czech Republic, Vinicna 7, 128 43, Prague, Czech Republic
  2. Biophysics Group, Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany
  3. Forschungszentrum Jülich GmbH, ICS-7, Biomechanics, Jülich, Germany
  
• ISSN：1420-9071

文摘

Focal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk-associated substrate (CAS) and vinculin, were both independently shown to be crucial for the ability of cells to transmit mechanical forces and to regulate cytoskeletal tension. Here, we identify a novel, direct binding interaction between CAS and vinculin. This interaction is mediated by the CAS SRC homology 3 domain and a proline-rich sequence in the hinge region of vinculin. We show that CAS localization in focal adhesions is partially dependent on vinculin, and that CAS–vinculin coupling is required for stretch-induced activation of CAS at the Y410 phosphorylation site. Moreover, CAS–vinculin binding significantly affects the dynamics of CAS and vinculin within focal adhesions as well as the size of focal adhesions. Finally, disruption of CAS binding to vinculin reduces cell stiffness and traction force generation. Taken together, these findings strongly implicate a crucial role of CAS–vinculin interaction in mechanosensing and focal adhesion dynamics.