Aurora-B phosphorylates the myosin II heavy chain to promote cytokinesis

Aryeh Babkoff,Einav Cohen-Kfir,Hananel Aharon,Shoshana Ravid

doi:10.1016/j.jbc.2021.101024

Abstract

Cytokinesis, the final step of mitosis, is mediated by an actomyosin contractile ring, the formation of which is temporally and spatially regulated following anaphase onset. Aurora-B is a member of the chromosomal passenger complex, which regulates various processes during mitosis; it is not understood, however, how Aurora-B is involved in cytokinesis. Here, we show that Aurora-B and myosin-IIB form a complex in vivo during telophase. Aurora-B phosphorylates the myosin-IIB rod domain at threonine 1847 (T1847), abrogating the ability of myosin-IIB monomers to form filaments. Furthermore, phosphorylation of myosin-IIB filaments by Aurora-B also promotes filament disassembly. We show that myosin-IIB possessing a phosphomimetic mutation at T1847 was unable to rescue cytokinesis failure caused by myosin-IIB depletion. Cells expressing a phosphoresistant mutation at T1847 had significantly longer intercellular bridges, implying that Aurora-B-mediated phosphorylation of myosin-IIB is important for abscission. We propose that myosin-IIB is a substrate of Aurora-B and reveal a new mechanism of myosin-IIB regulation by Aurora-B in the late stages of mitosis.

Highlights

In vertebrates, there are at least three nonmuscle myosin II (NMII) isoforms: NMIIA, NMIIB, and NMIIC [7,8,9]
As survivin interacts with Aurora-B [58] and NMIIB [19] during mitosis, we hypothesized that Aurora-B and NMIIB form a complex in vivo
We found that GFP-Aurora-B coimmunoprecipitated with endogenous NMIIB (Fig. 1A), forming a complex in vivo

Summary

Introduction

There are at least three NMII isoforms: NMIIA, NMIIB, and NMIIC [7,8,9]. Many studies have shown that different proteins can bind directly to NMII, regulating its filament assembly [11, 19,20,21] Another regulatory mechanism operates through the phosphorylation of NMII heavy and light chains [10]. Several studies using mammalian cells have shown that NMII heavy chains can be phosphorylated by different kinases, such as protein kinase C (PKC) and casein kinase II [11, 22,23,24] These phosphorylation events have been shown to regulate NMII functions, such as cellular localization, protein– protein interactions, and filament assembly [12, 24,25,26]. This is the first study demonstrating the role of NMII heavy chain phosphorylation by Aurora-B in the regulation of NMII during mitosis

Methods

Results

Conclusion