RT Journal Article
SR Electronic
T1 The cytoskeleton as a smart composite material: A unified pathway linking microtubules, myosin-II filaments and integrin adhesions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 195495
DO 10.1101/195495
A1 Nisha Bte Mohd Rafiq
A1 Yukako Nishimura
A1 Sergey V. Plotnikov
A1 Visalatchi Thiagarajan
A1 Zhen Zhang
A1 Meenubharathi Natarajan
A1 Shidong Shi
A1 Virgile Viasnoff
A1 Gareth E. Jones
A1 Pakorn Kanchanawong
A1 Alexander D. Bershadsky
YR 2018
UL http://biorxiv.org/content/early/2018/07/17/195495.abstract
AB 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 adhesions, 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. Myosin-IIA filaments, augmenting the focal adhesions and disrupting the podosomes, are indispensable effectors in the microtubule-dependent 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 capturing by integrin-mediated adhesions modulates the GEF-H1-dependent effect of microtubules on the myosin-IIA filaments. Subsequent actomyosin reorganization then remodels the focal adhesions and podosomes, closing the regulatory loop.