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

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

Author information

1
Mechanobiology Institute, National University of Singapore, Singapore, Singapore.
2
Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK.
3
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
4
CNRS UMI 3639, Singapore, Singapore.
5
Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
6
Mechanobiology Institute, National University of Singapore, Singapore, Singapore. biekp@nus.edu.sg.
7
Deparment of Biomedical Engineering, National University of Singapore, Singapore, Singapore. biekp@nus.edu.sg.
8
Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK. gareth.jones@kcl.ac.uk.
9
Mechanobiology Institute, National University of Singapore, Singapore, Singapore. alexander.bershadsky@weizmann.ac.il.
10
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. alexander.bershadsky@weizmann.ac.il.

Abstract

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.

PMID:
31114072
DOI:
10.1038/s41563-019-0371-y
[Indexed for MEDLINE]

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