TY - JOUR T1 - Microtubule regulation of integrin-based adhesions is mediated by myosin-IIA JF - bioRxiv DO - 10.1101/195495 SP - 195495 AU - Yukako Nishimura AU - Nisha Bte Mohd Rafiq AU - Sergey V. Plotnikov AU - Zhen Zhang AU - Visalatchi Thiagarajan AU - Meenubharathi Natarajan AU - Gareth E. Jones AU - Pakorn Kanchanawong AU - Alexander D. Bershadsky Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/09/28/195495.abstract N2 - The role of microtubules in the mechanoregulation of integrin-mediated adhesions is poorly understood. Here, we show that uncoupling of microtubules from integrin adhesions by depletion or displacement of KANK family proteins connecting the adhesion protein talin with microtubule tips led to disruption of podosomes and augmentation of focal adhesions, similarly to total disruption of microtubules. Using structured-illumination microscopy, we demonstrate that microtubule uncoupling from adhesions or total microtubule disruption brings about a massive assembly of myosin-IIA filaments, whilst a burst of microtubule polymerization led to a transient disassembly of myosin-IIA filaments. We showed that myosin-IIA filaments are indispensable for microtubule-dependent regulation of focal adhesions and podosomes. The microtubule-driven control of myosin-IIA filament formation is achieved through the regulation of Rho by microtubule-localized Rho guanine nucleotide exchange factor GEF-H1. Thus, a unifying mechanism of microtubule-mediated regulation of focal adhesions and podosomes operates via KANKs- and GEF-H1-dependent local reorganization of myosin-II filaments. ER -