Regulation and Assembly of Actomyosin Contractile Rings in Cytokinesis and Cell Repair

Abstract

Cytokinesis and single‐cell wound repair both involve contractile assemblies of filamentous actin (F‐actin) and myosin II organized into characteristic ring‐like arrays. The assembly of these actomyosin contractile rings (CRs) is specified spatially and temporally by small Rho GTPases, which trigger local actin polymerization and myosin II contractility via a variety of downstream effectors. We now have a much clearer view of the Rho GTPase signaling cascade that leads to the formation of CRs, but some factors involved in CR positioning, assembly, and function remain poorly understood. Recent studies show that this regulation is multifactorial and goes beyond the long‐established Ca2+‐dependent processes. There is substantial evidence that the Ca2+‐independent changes in cell shape, tension, and plasma membrane composition that characterize cytokinesis and single‐cell wound repair also regulate CR formation. Elucidating the regulation and mechanistic properties of CRs is important to our understanding of basic cell biology and holds potential for therapeutic applications in human disease. In this review, we present a primer on the factors influencing and regulating CR positioning, assembly, and contraction as they occur in a variety of cytokinetic and single‐cell wound repair models. Anat Rec, 301:2051–2066, 2018. © 2018 Wiley Periodicals, Inc.

The kinesin-like protein Pavarotti functions noncanonically to regulate actin dynamics

“…This model shares many features of cytokinesis, including an essential actomyosin contractile ring for wound closure and a requirement for MTs (Abreu-Blanco et al, 2011aNakamura et al, 2017Nakamura et al, , 2018. To date, our work and the work of others has elucidated a cassette of molecular factors involved in cell wound repair that is strikingly similar to those used during cytokinesis (Cooper and McNeil, 2015;Dekraker et al, 2018;Nakamura et al, 2018;Sonnemann and Bement, 2011). In addition to the actomyosin ring, Rho1, Rac1, and Cdc42 are essential to cell wound repair, where they exhibit distinct spatiotemporal patterns (Abreu-Blanco et al, 2014;Benink and Bement, 2005;Nakamura et al, 2017).…”

The kinesin-like protein Pavarotti functions non-canonically to regulate actin dynamics

“…This model shares many features of cytokinesis, including an essential actomyosin contractile ring that is necessary for wounds to close (Abreu-Blanco et al, 2011a; Abreu-Blanco et al, 2014; Nakamura et al, 2018; Nakamura et al, 2017). To date, our work and the work of others has elucidated a cassette of molecular factors involved in cell wound repair that is strikingly similar to those used during cytokinesis (Cooper and McNeil, 2015; Dekraker et al, 2018; Nakamura et al, 2018; Sonnemann and Bement, 2012). In addition to the actomyosin ring, Rho1, Rac1, and Cdc42 are essential to wound healing where they exhibit distinct spatiotemporal patterns (Abreu-Blanco et al, 2014; Benink and Bement, 2005; Nakamura et al, 2017).…”

“…Cytoskeletal elements must be temporally and spatially coordinated for cells to carry out complex functions, including cell division and cell wound repair (Abreu-Blanco et al, 2011b; Agarwal and Zaidel-Bar, 2019; Basant and Glotzer, 2018; Bement and von Dassow, 2014; Cheffings et al, 2016; Chew et al, 2017; Chugh and Paluch, 2018; D’Avino et al, 2015; Dekraker et al, 2018; Dogterom and Koenderink, 2019; Green et al, 2012; Nakamura et al, 2018; Pollard and O’Shaughnessy, 2019; Sonnemann and Bement, 2012; Verboon and Parkhurst, 2015). MTs form a radial array pattern and associate with actin around wounds in Xenopus oocytes (Mandato and Bement, 2003), whereas MTs do not accumulate or become spatially arrayed in the Drosophila cell wound repair model (Abreu-Blanco et al, 2011a).…”

A Simple and Robust Cell-Based Assay for the Discovery of Novel Cytokinesis Inhibitors

“…In animals, a contractile ring of filamentous actin and nonmuscle myosin II (NMII) assembles in the equatorial plane of the dividing cells (between the segregated sister chromatids) that splits the cytoplasm during cytokinesis by forming the so-called cleavage furrow. The process is tightly regulated both in space and time in a cell-type specific manner [2][3][4][5] . Cytokinesis inhibitors targeting actin, myosin or other regulatory and structural elements necessary for the proper functioning of the cleavage furrow have not only provided useful information about the function of these elements, but are increasingly recognized as potential drug candidates 6 .…”