Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41563-019-0371-y
Title: A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions
Authors: Rafiq, Nisha Bte Mohd 
Nishimura, Yukako 
Plotnikov, Sergey V
Thiagarajan, Visalatchi 
Zhang, Zhen 
Shi, Shidong 
Natarajan, Meenubharathi 
Viasnoff, Virgile 
Kanchanawong, Pakorn 
Jones, Gareth E 
Bershadsky, Alexander D 
Keywords: Science & Technology
Physical Sciences
Technology
Chemistry, Physical
Materials Science, Multidisciplinary
Physics, Applied
Physics, Condensed Matter
Chemistry
Materials Science
Physics
NUCLEOTIDE EXCHANGE FACTOR
ACTIN STRESS FIBERS
NANOSCALE ARCHITECTURE
DEPENDENT FORMATION
FOCAL ADHESIONS
CELL
GEF-H1
RHO
PODOSOMES
BINDING
Issue Date: 1-Jun-2019
Publisher: NATURE PUBLISHING GROUP
Citation: Rafiq, Nisha Bte Mohd, Nishimura, Yukako, Plotnikov, Sergey V, Thiagarajan, Visalatchi, Zhang, Zhen, Shi, Shidong, Natarajan, Meenubharathi, Viasnoff, Virgile, Kanchanawong, Pakorn, Jones, Gareth E, Bershadsky, Alexander D (2019-06-01). A mechano-signalling network linking microtubules, myosin IIA filaments and integrin-based adhesions. NATURE MATERIALS 18 (6) : 638-+. ScholarBank@NUS Repository. https://doi.org/10.1038/s41563-019-0371-y
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.
Source Title: NATURE MATERIALS
URI: https://scholarbank.nus.edu.sg/handle/10635/194071
ISSN: 14761122
14764660
DOI: 10.1038/s41563-019-0371-y
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