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

Shuangshuang Zhao; Xuemeng Shi; Yue Zhang; Zeyu Wen; Jinping Cai; Wei Gao; Jiayi Xu; Yifei Zheng; Baohua Ji; Yanqin Cui; Kun Shi; Yanjun Liu; Hui Li; Yaming Jiu

doi:10.1016/j.isci.2020.100975

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

iScience. 2020 Apr 24;23(4):100975. doi: 10.1016/j.isci.2020.100975. Epub 2020 Mar 11.

Authors

Shuangshuang Zhao¹, Xuemeng Shi¹, Yue Zhang², Zeyu Wen², Jinping Cai³, Wei Gao², Jiayi Xu⁴, Yifei Zheng⁴, Baohua Ji⁴, Yanqin Cui¹, Kun Shi¹, Yanjun Liu⁵, Hui Li⁶, Yaming Jiu⁷

Affiliations

¹ The Joint Program in Infection and Immunity, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623; Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
² The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing 100049, China.
³ The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
⁴ Institute of Applied Mechanics, Zhejiang University, Hangzhou 310027, China.
⁵ Shanghai Institute of Cardiovascular Diseases, and Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁶ University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing 100049, China; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
⁷ The Joint Program in Infection and Immunity, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623; Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing 100049, China. Electronic address: ymjiu@ips.ac.cn.

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.

Keywords: Biological Sciences; Cell Biology; Functional Aspects of Cell Biology.