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Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers.


ABSTRACT: Actin stress fibers guide cell migration and morphogenesis. During centripetal flow, actin transverse arcs fuse accompanied by the formation of myosin II stacks to generate mechanosensitive actomyosin bundles. However, whether myosin II stack formation plays a role in cell mechano-sensing has remained elusive. Myosin-18B is a "glue" molecule for assembling myosin II stacks. By examining actin networks and traction forces, we find that cells abolishing myosin-18B resemble Ca2+?calmodulin-dependent kinase kinase 2 (CaMKK2)-defective cells. Inhibition of CaMKK2 activity reverses the strong actin network to thin filaments in myosin-18B-overexpressing cells. Moreover, AMP-activated protein kinase (AMPK) activation is able to relieve the thin stress fibers by myosin-18B knockout. Importantly, lack of myosin-18B compromises AMPK-vasodilator-stimulated phosphoprotein and RhoA-myosin signaling, thereby leading to defective persistent migration, which can be rescued only by full-length and C-extension-less myosin-18B. Together, these results reveal a critical role of myosin-18B in the mechanosensitive regulation of migrating cells.

SUBMITTER: Zhao S 

PROVIDER: S-EPMC7109629 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers.

Zhao Shuangshuang S   Shi Xuemeng X   Zhang Yue Y   Wen Zeyu Z   Cai Jinping J   Gao Wei W   Xu Jiayi J   Zheng Yifei Y   Ji Baohua B   Cui Yanqin Y   Shi Kun K   Liu Yanjun Y   Li Hui H   Jiu Yaming Y  

iScience 20200311 4


Actin stress fibers guide cell migration and morphogenesis. During centripetal flow, actin transverse arcs fuse accompanied by the formation of myosin II stacks to generate mechanosensitive actomyosin bundles. However, whether myosin II stack formation plays a role in cell mechano-sensing has remained elusive. Myosin-18B is a "glue" molecule for assembling myosin II stacks. By examining actin networks and traction forces, we find that cells abolishing myosin-18B resemble Ca<sup>2+</sup>∕calmodul  ...[more]

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