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

Summary: 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 h...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2020-04-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220301590
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author 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
author_facet 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
author_sort Shuangshuang Zhao
collection DOAJ
description Summary: 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. : Biological Sciences; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Functional Aspects of Cell Biology
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spelling doaj.art-89c86dfc7efb4cb9b951019f062389ed2022-12-22T03:53:14ZengElsevieriScience2589-00422020-04-01234Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress FibersShuangshuang Zhao0Xuemeng Shi1Yue Zhang2Zeyu Wen3Jinping Cai4Wei Gao5Jiayi Xu6Yifei Zheng7Baohua Ji8Yanqin Cui9Kun Shi10Yanjun Liu11Hui Li12Yaming Jiu13The 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, ChinaThe 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, ChinaThe 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, ChinaThe 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, ChinaThe Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, ChinaThe 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, ChinaInstitute of Applied Mechanics, Zhejiang University, Hangzhou 310027, ChinaInstitute of Applied Mechanics, Zhejiang University, Hangzhou 310027, ChinaInstitute of Applied Mechanics, Zhejiang University, Hangzhou 310027, ChinaThe 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, ChinaThe 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, ChinaShanghai Institute of Cardiovascular Diseases, and Institutes of Biomedical Sciences, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaUniversity 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, ChinaThe 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; Corresponding authorSummary: 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. : Biological Sciences; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Functional Aspects of Cell Biologyhttp://www.sciencedirect.com/science/article/pii/S2589004220301590
spellingShingle 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
Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers
iScience
title Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers
title_full Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers
title_fullStr Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers
title_full_unstemmed Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers
title_short Myosin-18B Promotes Mechanosensitive CaMKK2-AMPK-VASP Regulation of Contractile Actin Stress Fibers
title_sort myosin 18b promotes mechanosensitive camkk2 ampk vasp regulation of contractile actin stress fibers
url http://www.sciencedirect.com/science/article/pii/S2589004220301590
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