Focal adhesions are controlled by microtubules through local contractility regulation

Julien Aureille, Srinivas S. Prabhu, Sam F. Barnett, Aaron J. Farrugia, Isabelle Arnal, Laurence Lafanechère, Boon Chuan Low, Pakorn Kanchanawong, Alex Mogilner, Alexander D. Bershadsky

Research output: Contribution to journalArticlepeer-review

Abstract

Microtubules regulate cell polarity and migration via local activation of focal adhesion turnover, but the mechanism of this process is insufficiently understood. Molecular complexes containing KANK family proteins connect microtubules with talin, the major component of focal adhesions. Here, local optogenetic activation of KANK1-mediated microtubule/talin linkage promoted microtubule targeting to an individual focal adhesion and subsequent withdrawal, resulting in focal adhesion centripetal sliding and rapid disassembly. This sliding is preceded by a local increase of traction force due to accumulation of myosin-II and actin in the proximity of the focal adhesion. Knockdown of the Rho activator GEF-H1 prevented development of traction force and abolished sliding and disassembly of focal adhesions upon KANK1 activation. Other players participating in microtubule-driven, KANK-dependent focal adhesion disassembly include kinases ROCK, PAK, and FAK, as well as microtubules/focal adhesion-associated proteins kinesin-1, APC, and αTAT. Based on these data, we develop a mathematical model for a microtubule-driven focal adhesion disruption involving local GEF-H1/RhoA/ROCK-dependent activation of contractility, which is consistent with experimental data.

Original languageEnglish (US)
JournalEMBO Journal
DOIs
StateAccepted/In press - 2024

Keywords

  • Focal Adhesion Mechanosensitivity
  • GEF-H1
  • iLID Optogenetics
  • KANK1
  • Myosin-II

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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