Mechanosensitive accumulation of non-muscle myosin IIB during mitosis requires its translocation activity

Chao Wang; Jingjing Ding; Qiaodong Wei; Shoukang Du; Xiaobo Gong; Ting Gang Chew

doi:10.1016/j.isci.2023.107773

Mechanosensitive accumulation of non-muscle myosin IIB during mitosis requires its translocation activity

iScience. 2023 Aug 29;26(10):107773. doi: 10.1016/j.isci.2023.107773. eCollection 2023 Oct 20.

Authors

Chao Wang^{1

2}, Jingjing Ding^{1

2}, Qiaodong Wei³, Shoukang Du^{1

2}, Xiaobo Gong³, Ting Gang Chew^{1

2}

Affiliations

¹ Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China.
² The Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China.
³ Department of Engineering Mechanics, School of Naval Architecture, Ocean and Civil Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Abstract

Non-muscle myosin II (NMII) is a force-generating mechanosensitive enzyme that responds to mechanical forces. NMIIs mechanoaccumulate at the cell cortex in response to mechanical forces. It is essential for cells to mechanically adapt to the physical environment, failure of which results in mitotic defects when dividing in confined environment. Much less is known about how NMII mechanoaccumulation is regulated during mitosis. We show that mitotic cells respond to compressive stress by promoting accumulation of active RhoA at the cell cortex as in interphase cells. RhoA mechanoresponse during mitosis activates and stabilizes NMIIB via ROCK signaling, leading to NMIIB mechanoaccumulation at the cell cortex. Using disease-related myosin II mutations, we found that NMIIB mechanoaccumulation requires its motor activity that translocates actin filaments, but not just its actin-binding function. Thus, the motor activity coordinates structural movement and nucleotide state changes to fine-tune actin-binding affinity optimal for NMIIs to generate and respond to forces.

Keywords: Developmental biology; Mechanobiology; Molecular biology.