| Literature DB >> 31114072 |
Nisha Bte Mohd Rafiq1,2, Yukako Nishimura1, Sergey V Plotnikov3, Visalatchi Thiagarajan1, Zhen Zhang1, Shidong Shi1, Meenubharathi Natarajan1, Virgile Viasnoff1,4,5, Pakorn Kanchanawong6,7, Gareth E Jones8, Alexander D Bershadsky9,10.
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.Entities:
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Year: 2019 PMID： 31114072 DOI： 10.1038/s41563-019-0371-y
Source DB: PubMed Journal: Nat Mater ISSN： 1476-1122 Impact factor: 43.841