The role of the interaction of the vinculin proline-rich linker region with vinexin α in sensing the stiffness of the extracellular matrix

Hiroshi Yamashita, Takafumi Ichikawa, Daisuke Matsuyama, Yasuhisa Kimura, Kazumitsu Ueda, Susan W. Craig, Ichiro Harada, Noriyuki Kioka

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Although extracellular matrix (ECM) stiffness is an important aspect of the extracellular microenvironment and is known to direct the lineage specification of stem cells and affect cancer progression, the molecular mechanisms that sense ECM stiffness have not yet been elucidated. In this study, we show that the proline-rich linker (PRL) region of vinculin and the PRL-region-binding protein vinexin are involved in sensing the stiffness of ECM substrates. A rigid substrate increases the level of cytoskeleton-associated vinculin, and the fraction of vinculin stably localizing at focal adhesions (FAs) is larger on rigid ECM than on soft ECM. Mutations in the PRL region or the depletion of vinexin expression impair these responses to ECM stiffness. Furthermore, vinexin depletion impairs the stiffness-dependent regulation of cell migration. These results suggest that the interaction of the PRL region of vinculin with vinexin a plays a crucial role in sensing ECM stiffness and in mechanotransduction.

Original languageEnglish (US)
Pages (from-to)1875-1886
Number of pages12
JournalJournal of cell science
Volume127
Issue number9
DOIs
StatePublished - May 2014

Keywords

  • Extracellular matrix
  • Mechanotransduction
  • Stiffness
  • Vinculin

ASJC Scopus subject areas

  • Cell Biology

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