Trends in Cell Biology
ReviewKnowing when to cut and run: mechanisms that control cytokinetic abscission
Section snippets
Cytokinesis and abscission are highly regulated
In animal cells, after nuclear envelope breakdown and chromosome separation during mitosis, cytokinesis leads to the partition of a single cell into two daughter cells. Cytokinesis begins with ingression of the cleavage furrow mediated by contraction of the actomyosin ring. As furrowing progresses, the spindle midzone (see Glossary) transforms into an intercellular bridge or midbody that connects the two dividing cells. The midbody contains antiparallel arrays of microtubules that meet at the
Mechanistic insights into abscission
Although most of the early cytokinetic events that precede furrow ingression and midbody formation have been widely studied, we have only recently started to understand the molecular mechanisms that contribute to the later steps of cytokinesis and abscission (Figure 1).
The midbody serves as a platform to orchestrate the cytoskeleton rearrangements, plasma membrane remodeling, and recruitment of the functional complexes needed for abscission. Before abscission occurs, a secondary ingression site
Membrane dynamics and cytoskeleton changes required for abscission
Local changes of specific phosphoinositides (PtdIns) at the cleavage furrow and midbody membrane are essential to modulate the recruitment and activity of several proteins needed for cytokinesis. Accordingly, phosphatidylinositol-3-monophosphate (PtdIns(3)P)-positive endosomes localize to the midbody during cytokinesis and depletion of the VPS34 or Beclin 1 subunits of the class III phosphatidylinositol-3-OH kinase (PtdIns3K-III), which mediates PtdIns(3)P formation, results in cytokinesis
Controlling abscission timing by ordered recruitment of the abscission machinery
It has become increasingly apparent that the spatiotemporal coordination of the events described above is essential for completion of cytokinesis. Two proteins recently found to be involved in abscission regulation are discussed in this section, namely CEP55 and MITD1. The timely recruitment of CEP55 after furrow ingression is essential to ensure the correct midbody architecture [45]. Subsequently, MITD1 may serve two purposes in the events leading to abscission 46, 47, by increasing midbody
Regulation of abscission timing by the NoCut pathway
Before cytokinesis starts, chromosomes need to be fully cleared from the cleavage plane to avoid being damaged during furrow formation [55]. Similarly, abscission must occur only after the complete separation of sister chromatids, because erroneous chromosome segregation can lead to aberrant cytokinesis resulting in the formation of tetraploid cells and cancer 56, 57. Therefore, to protect cells against genomic instability and its deleterious effects, a surveillance mechanism or checkpoint is
An intriguing connection between nuclear pores and abscission control
An alternative way of activating an Aurora B-dependent abscission delay that involves the nuclear pore has been found in human cells. Following mitotic DNA segregation and cytokinesis initiation, the chromosomes are decondensed and the nuclear envelope is reformed. The nucleoporins (Nup) ELYS/MEL-28, Nup153, and Nup50 are rapidly recruited to the decondensing chromatin and aid in the recruitment of membranes to form the nuclear envelope and other Nup subunits, which rapidly assemble into
Concluding remarks
The last few years have seen rapid and exciting advances in our understanding of the various molecular mechanisms regulating cytokinetic abscission. Despite the original idea of cells separating by simply rupturing their midbodies, it is now clear that abscission is a complex and extremely regulated process that requires a myriad of cellular functions, including vesicle trafficking, cytoskeletal rearrangements, and a machinery that mediates membrane scission. Live-cell imaging by time-lapse
Acknowledgments
The authors thank Anna Caballe, Leticia Labrador, and Stuart Neil for critical comments on the manuscript. J.M-S. is funded by the Medical Research Council (G0802777), the Lister Institute for Preventative Medicine, and the EMBO Young Investigator Program. J.M-S. and M.A. are funded by a Wellcome Trust grant (WT093056MA).
Glossary
- Apoptosis-linked gene-2-interacting protein X (ALIX)
- cytoplasmic protein first characterized as a binding partner of ALG-2. ALIX is also an ESCRT-associated protein that functions in cytokinesis by recruiting ESCRT-III to the midbody.
- Central spindle
- region at the center of the spindle midzone that originates the intercellular bridge or midbody. Among other proteins, central spindle assembly requires the central spindlin complex, which comprises the kinesin-like protein MKLP1 and the Rho family
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2020, International ImmunopharmacologyCitation Excerpt :Previous reports support the idea that the ESCRT-III complex mediates the final membrane fission that is essential for abscission. Consequently, in cells with altered ESCRT-III regulation and function, cancer can develop as a result of aberrant cytokinesis [35]. Furthermore, previous results suggested that ESCRT-III dysregulation of abscission could cause tumorigenesis and genetic instability if it synergizes with mitotic stress brought upon by oncogenes [17].
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2019, Fungal Genetics and BiologyCitation Excerpt :Mitotic chromatin bridges of late segregating chromosome arms have been observed across the eukarya. To prevent chromosome breakage, in many organisms the Aurora B kinase localizes to the spindle midzone as part of a post-anaphase checkpoint that responds to lagging chromosomes (Agromayor and Martin-Serrano, 2013; Steigemann and Gerlich, 2009; Steigemann et al., 2009). This abscission checkpoint (or no-cut pathway in yeast) ensures that cytokinesis is not completed until chromatin bridges have been resolved in uninucleated species (Mendoza et al., 2009; Norden et al., 2006).