Adhesion-dependent and Contractile Ring-independent Equatorial Furrowing during Cytokinesis in Mammalian Cells

Kanada, Masamitsu; Nagasaki, Akira; Uyeda, Taro Q.P.

doi:10.1091/mbc.e05-03-0233

Cited by 88 publications

(101 citation statements)

References 42 publications

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“…Clearly, focusing is not absolutely essential for cytokinesis in situations where either myosin-2 or Rho is inhibited. (71,72) However, when cytokinesis is monitored in living epithelial cells or epithelia in situ, until the terminal phase of the process, the cytokinetic apparatus is tightly focused, cutting through the cell like a knife. Moreover, broad cytokinetic arrays are associated with inefficient furrowing, (20) implying that focusing is important.…”

Section: Contributions Of the Zones To Contractile Arraysmentioning

confidence: 99%

Rho GTPase activity zones and transient contractile arrays

2006

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SummaryThe Rho GTPases-Rho, Rac and Cdc42-act as molecular switches, cycling between an active GTP-bound state and an inactive GDP-bound state, to regulate the actin cytoskeleton. It has recently become apparent that the Rho GTPases can be activated in subcellular zones that appear semi-stable, yet are dynamically maintained. These Rho GTPase activity zones are associated with a variety of fundamental biological processes including symmetric and asymmetric cytokinesis and cellular wound repair. Here we review the basic features of Rho GTPase activity zones, suggest that these zones represent a fundamental signaling mechanism, and discuss the implications of zone properties from the perspective of both their function and how they are likely to be controlled.

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Section: Contributions Of the Zones To Contractile Arraysmentioning

confidence: 99%

Rho GTPase activity zones and transient contractile arrays

2006

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“…In the present study, we explored the functions of Ect2 in mammalian cytokinesis A and B using HeLa cells, which rely on cytokinesis A for division, and HT1080 human fibrosarcoma cells, which are able to divide using cytokinesis B when cytokinesis A is inhibited (Kanada et al, 2005). Our findings provide the first direct evidence that Ect2 is dispensable for cytokinesis in certain types of mammalian cells and that RhoA localized at the equatorial cortex is indirectly required for the maintenance of appropriate polar lamellipodia formation in mitotic cells undergoing cytokinesis B.…”

Section: Introductionmentioning

confidence: 99%

“…This process was named "attachment-assisted mitotic cleavage" (Neujahr et al, 1997) or "cytokinesis B" to distinguish it from "cytokinesis A," which refers to the adhesionindependent, contractile ring-dependent "classic" cytokinesis (Zang et al, 1997;Nagasaki et al, 2002). On highly adherent substrates, certain types of mammalian cells are also able to divide in an adhesion-dependent, contractile ring-independent manner when the activity of the contractile ring is blocked by the myosin II-specific inhibitor blebbistatin (Kanada et al, 2005). In addition, Burton and Taylor (1997) reported a case of successful division of a fibroblast that was driven by traction forces after regression of the initial equatorial furrow under physiological culture condi- tions.…”

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confidence: 99%

“…This observation can be interpreted to mean that cytokinesis B is activated when cells fail to properly complete cytokinesis A and that mammalian cytokinesis B serves as a backup mechanism. In that case, adherent mammalian cells capable of cytokinesis B must have a mechanism that enables them to make use of cytokinesis A or B to ensure successful cell division.In the present study, we explored the functions of Ect2 in mammalian cytokinesis A and B using HeLa cells, which rely on cytokinesis A for division, and HT1080 human fibrosarcoma cells, which are able to divide using cytokinesis B when cytokinesis A is inhibited (Kanada et al, 2005). Our findings provide the first direct evidence that Ect2 is dispensable for cytokinesis in certain types of mammalian cells and that RhoA localized at the equatorial cortex is indirectly required for the maintenance of appropriate polar lamellipodia formation in mitotic cells undergoing cytokinesis B.…”

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confidence: 99%

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Novel Functions of Ect2 in Polar Lamellipodia Formation and Polarity Maintenance during “Contractile Ring-Independent” Cytokinesis in Adherent Cells

Kanada

Nagasaki

Uyeda

2008

MBoC

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Some mammalian cells are able to divide via both the classic contractile ring-dependent method (cytokinesis A) and a contractile ring-independent, adhesion-dependent method (cytokinesis B). Cytokinesis A is triggered by RhoA, which, in HeLa cells, is activated by the guanine nucleotide-exchange factor Ect2 localized at the central spindle and equatorial cortex. Here, we show that in HT1080 cells undergoing cytokinesis A, Ect2 does not localize in the equatorial cortex, though RhoA accumulates there. Moreover, Ect2 depletion resulted in only modest multinucleation of HT1080 cells, enabling us to establish cell lines in which Ect2 was constitutively depleted. Thus, RhoA is activated via an Ect2-independent pathway during cytokinesis A in HT1080 cells. During cytokinesis B, Ect2-depleted cells showed narrower accumulation of RhoA at the equatorial cortex, accompanied by compromised pole-to-equator polarity, formation of ectopic lamellipodia in regions where RhoA normally would be distributed, and delayed formation of polar lamellipodia. Furthermore, C3 exoenzyme inhibited equatorial RhoA activation and polar lamellipodia formation. Conversely, expression of dominant active Ect2 in interphase HT1080 cells enhanced RhoA activity and suppressed lamellipodia formation. These results suggest that equatorial Ect2 locally suppresses lamellipodia formation via RhoA activation, which indirectly contributes to restricting lamellipodia formation to polar regions during cytokinesis B. INTRODUCTIONThe final step in the process of cell division is cytokinesis, during which the cellular contents are divided and the two daughter cells are formed. Formation of the furrow that ultimately leads to separation of the two daughter cells is mediated in large part by RhoA (Kishi et al., 1993;Mabuchi et al., 1993;Jantsch-Plunger et al., 2000), one of the Rho-type small GTPases, which also include Rac1 and Cdc42; these mediators regulate actin dynamics during a variety of cellular events (reviewed by Etienne-Manneville and Hall, 2002). In the classic "purse string" model of cytokinesis, actomyosin-dependent contraction of the contractile ring drives cleavage of the equatorial region (reviewed by Glotzer, 2005). RhoA-dependent stimulation of actin polymerization through regulation of formins is crucial to formation of the contractile ring (Sagot et al., 2002;Kovar et al., 2003), while phosphorylation of myosin light chain by Rhoassociated kinase (ROCK) leads to myosin activation and contraction of the ring (Amano et al., 1996;Kimura et al., 1996;Piekny and Mains, 2002;Matsumura, 2005).Rho GTPases are activated by guanine nucleotide exchange factors (GEFs). Among the numerous GEFs that have been identified, Ect2 (Epithelial cell transforming protein 2) has been shown to play a key role in cytokinesis. Ect2 was originally identified as a transforming protein in an expression-cloning assay (Miki et al., 1993). Its role in cytokinesis was first identified in studies of Drosophila melanogaster. The Drosophila and Caenorhabditis elegans orthologue...

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“…For example, by providing membrane-cortex linkages, myosin I motors contribute significantly to cortical tension (23). Myosin II-independent cytokinesis is not restricted to Dictyostelium, and likely explains how mammalian cells can divide with myosin II inhibition if the adhesion conditions are appropriate (24), and in tissues when the myosin II-actin-bound state is sufficiently prolonged to last through an entire cytokinesis furrow ingression event (25).…”

Section: Forces Acting On the Cell Cortexmentioning

confidence: 99%

Mechanochemical Signaling Directs Cell-Shape Change

Schiffhauer

Robinson

2017

Biophysical Journal

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For specialized cell function, as well as active cell behaviors such as division, migration, and tissue development, cells must undergo dynamic changes in shape. To complete these processes, cells integrate chemical and mechanical signals to direct force production. This mechanochemical integration allows for the rapid production and adaptation of leading-edge machinery in migrating cells, the invasion of one cell into another during cell-cell fusion, and the force-feedback loops that ensure robust cytokinesis. A quantitative understanding of cell mechanics coupled with protein dynamics has allowed us to account for furrow ingression during cytokinesis, a model cell-shape-change process. At the core of cell-shape changes is the ability of the cell's machinery to sense mechanical forces and tune the force-generating machinery as needed. Force-sensitive cytoskeletal proteins, including myosin II motors and actin cross-linkers such as a-actinin and filamin, accumulate in response to internally generated and externally imposed mechanical stresses, endowing the cell with the ability to discern and respond to mechanical cues. The physical theory behind how these proteins display mechanosensitive accumulation has allowed us to predict paralogspecific behaviors of different cross-linking proteins and identify a zone of optimal actin-binding affinity that allows for mechanical stress-induced protein accumulation. These molecular mechanisms coupled with the mechanical feedback systems ensure robust shape changes, but if they go awry, they are poised to promote disease states such as cancer cell metastasis and loss of tissue integrity.The concept ''form begets function begets form'' provides an excellent foundation for understanding the behavior of biological systems. Even specialized cells, the smallest unit of complex living systems, perform all of the necessary functions of an organism by assuming distinct shapes, mechanical properties, and physical behaviors. Different cell types use a common set of cytoskeletal elements to provide precise physical support for their distinct functions. For example, red blood cells and neurons have very different shapes that allow them to perform their specific roles. However, they both utilize alternating patterns of actin and spectrin to form cortices with appropriate viscous and elastic properties, albeit in different structural arrangements. Perturbations to this structural network cause a breakdown in the mechanical properties, or the form, of these cells, which inhibits cell function (1,2).Fascinatingly, the physical properties of cells are both determined and acted upon by the cytoskeletal apparatus. Cells are capable of modifying their own physical properties and driving changes in cell shape in response to internal and external chemical and mechanical stimuli. These modifications occur through the remodeling of the cell cortex, the network of cytoskeletal proteins directly under the plasma membrane. Much progress has been made recently in deciphering how chemical signa...

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Adhesion-dependent and Contractile Ring-independent Equatorial Furrowing during Cytokinesis in Mammalian Cells

Cited by 88 publications

References 42 publications

Rho GTPase activity zones and transient contractile arrays

Rho GTPase activity zones and transient contractile arrays

Novel Functions of Ect2 in Polar Lamellipodia Formation and Polarity Maintenance during “Contractile Ring-Independent” Cytokinesis in Adherent Cells

Mechanochemical Signaling Directs Cell-Shape Change

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