A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions

Nat Mater. 2019 Jun;18(6):638-649. doi: 10.1038/s41563-019-0371-y. Epub 2019 May 21.


The interrelationship between microtubules and the actin cytoskeleton in mechanoregulation of integrin-mediated adhesions is poorly understood. Here, we show that the effects of microtubules on two major types of cell-matrix adhesion, focal adhesions and podosomes, are mediated by KANK family proteins connecting the adhesion protein talin with microtubule tips. Both total microtubule disruption and microtubule uncoupling from adhesions by manipulations with KANKs trigger a massive assembly of myosin IIA filaments, augmenting focal adhesions and disrupting podosomes. Myosin IIA filaments are indispensable effectors in the microtubule-driven regulation of integrin-mediated adhesions. Myosin IIA filament assembly depends on Rho activation by the RhoGEF GEF-H1, which is trapped by microtubules when they are connected with integrin-mediated adhesions via KANK proteins but released after their disconnection. Thus, microtubule capture by integrin-mediated adhesions modulates the GEF-H1-dependent effect of microtubules on the assembly of myosin IIA filaments. Subsequent actomyosin reorganization then remodels the focal adhesions and podosomes, closing the regulatory loop.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cytoskeletal Proteins
  • Focal Adhesions / metabolism*
  • Humans
  • Integrins / metabolism*
  • Mechanotransduction, Cellular
  • Microtubules / metabolism*
  • Nonmuscle Myosin Type IIA / metabolism*
  • Podosomes / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Rho Guanine Nucleotide Exchange Factors / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • rho GTP-Binding Proteins / metabolism
  • rho-Associated Kinases / metabolism


  • ARHGEF2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Integrins
  • KANK1 protein, human
  • Kank2 protein, human
  • Recombinant Proteins
  • Rho Guanine Nucleotide Exchange Factors
  • Tumor Suppressor Proteins
  • rho-Associated Kinases
  • Nonmuscle Myosin Type IIA
  • rho GTP-Binding Proteins