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

Research output: Contribution to journalArticlepeer-review

Nisha Bte Mohd Rafiq, Yukako Nishimura, Sergey V. Plotnikov, Visalatchi Thiagarajan, Zhen Zhang, Shidong Shi, Meenubharathi Natarajan, Virgile Viasnoff, Pakorn Kanchanawong, Gareth E Jones, Alexander D. Bershadsky

Original languageEnglish
Pages (from-to)638-649
Number of pages12
JournalNATURE MATERIALS
Volume18
Issue number6
Early online date21 May 2019
DOIs
Accepted/In press10 Apr 2019
E-pub ahead of print21 May 2019
Published1 Jun 2019

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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.

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