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Molecular Factors and Mechanisms Involved in Cytokinesis II
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Molecular Factors and Mechanisms Involved in Cytokinesis II

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Proliferation and Division".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 15752

Special Issue Editor

Dr. Maria Grazia Giansanti

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Guest Editor
Consiglion Nazionale delle Ricerche, Istituto di Biologia e Patologia Molecolari c/o Dipartimento di Biologia e Biotecnologie, Università Sapienza di Roma, Piazzale A. Moro 5, 00185 Roma, Italy
Interests: membrane trafficking; cytokinesis; Drosophila melanogaster; mitosis; male meiosis; congenital disorders of glycosylation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Guest Editor invites you to contribute to this Special Issue dedicated to the mechanisms and molecular factors that regulate cytokinesis. Cytokinesis, the final step of the cell cycle, separates the duplicated genome and the cytoplasmic content of the dividing cell equitably into two daughters. This process must be finely regulated in space and time for proper development and to maintain the normal ploidy in adult issues. In animal cells, the contractile ring—a dynamic structure composed of F-actin filaments and active myosin II—is assembled just beneath the plasma membrane around the cell equator of dividing anaphase cells. Constriction of the contractile ring pulls the plasma membrane and the underlying cortex inward, leading to the formation of a cleavage furrow. Furrow ingression proceeds until the two daughter cells remain connected by a thin cytoplasmic bridge which contains in its center an organelle dubbed the midbody. Abscission, the final step of cytokinesis, is orchestrated by the coordinated activities of several protein complexes in the midbody, generating two fully separated daughter cells. Much has been learned on the molecular machinery required for the formation, constriction and disassembly of the contractile apparatus. However, many questions remain open. 

This Special Issue will increase our knowledge of an intricate process, requiring at least one hundred proteins and a dynamic interplay between actin filaments, microtubules and membranes. Dysregulation of cytokinesis leads to a number of human diseases, such as blood disorders, Lowe syndrome, female infertility, and cancer. Thus, studies on the underlying molecular mechanisms of cytokinesis might contribute to the identification of new therapeutic targets for human disease.

Dr. Maria Grazia Giansanti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • contractile ring
  • midbody
  • abscission
  • membrane trafficking
  • model organisms

Related Special Issue

Published Papers (5 papers)

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Research

Jump to: Review

17 pages, 3633 KiB  
Article
High-Content RNAi Phenotypic Screening Unveils the Involvement of Human Ubiquitin-Related Enzymes in Late Cytokinesis
by Mikaël Boullé, Laurianne Davignon, Keïs Nabhane Saïd Halidi, Salomé Guez, Emilie Giraud, Marcel Hollenstein and Fabrice Agou
Cells 2022, 11(23), 3862; https://doi.org/10.3390/cells11233862 - 30 Nov 2022
Cited by 1 | Viewed by 1780
Abstract
CEP55 is a central regulator of late cytokinesis and is overexpressed in numerous cancers. Its post-translationally controlled recruitment to the midbody is crucial to the structural coordination of the abscission sequence. Our recent evidence that CEP55 contains two ubiquitin-binding domains was the first [...] Read more.
CEP55 is a central regulator of late cytokinesis and is overexpressed in numerous cancers. Its post-translationally controlled recruitment to the midbody is crucial to the structural coordination of the abscission sequence. Our recent evidence that CEP55 contains two ubiquitin-binding domains was the first structural and functional link between ubiquitin signaling and ESCRT-mediated severing of the intercellular bridge. So far, high-content screens focusing on cytokinesis have used multinucleation as the endpoint readout. Here, we report an automated image-based detection method of intercellular bridges, which we applied to further our understanding of late cytokinetic signaling by performing an RNAi screen of ubiquitin ligases and deubiquitinases. A secondary validation confirmed four candidate genes, i.e., LNX2, NEURL, UCHL1 and RNF157, whose downregulation variably affects interconnected phenotypes related to CEP55 and its UBDs, as follows: decreased recruitment of CEP55 to the midbody, increased number of midbody remnants per cell, and increased frequency of intercellular bridges or multinucleation events. This brings into question the Notch-dependent or independent contributions of LNX2 and NEURL proteins to late cytokinesis. Similarly, the role of UCHL1 in autophagy could link its function with the fate of midbody remnants. Beyond the biological interest, this high-content screening approach could also be used to isolate anticancer drugs that act by impairing cytokinesis and CEP55 functions. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis II)
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13 pages, 12110 KiB  
Communication
Midbody Proteins Display Distinct Dynamics during Cytokinesis
by Ella F. J. Halcrow, Riccardo Mazza, Anna Diversi, Anton Enright and Pier Paolo D’Avino
Cells 2022, 11(21), 3337; https://doi.org/10.3390/cells11213337 - 22 Oct 2022
Cited by 4 | Viewed by 2212
Abstract
The midbody is an organelle that forms between the two daughter cells during cytokinesis. It co-ordinates the abscission of the nascent daughter cells and is composed of a multitude of proteins that are meticulously arranged into distinct temporal and spatial localization patterns. However, [...] Read more.
The midbody is an organelle that forms between the two daughter cells during cytokinesis. It co-ordinates the abscission of the nascent daughter cells and is composed of a multitude of proteins that are meticulously arranged into distinct temporal and spatial localization patterns. However, very little is known about the mechanisms that regulate the localization and function of midbody proteins. Here, we analyzed the temporal and spatial profiles of key midbody proteins during mitotic exit under normal conditions and after treatment with drugs that affect phosphorylation and proteasome-mediated degradation to decipher the impacts of post-translational modifications on midbody protein dynamics. Our results highlighted that midbody proteins show distinct spatio-temporal dynamics during mitotic exit and cytokinesis that depend on both ubiquitin-mediated proteasome degradation and phosphorylation/de-phosphorylation. They also identified two discrete classes of midbody proteins: ‘transient’ midbody proteins—including Anillin, Aurora B and PRC1—which rapidly accumulate at the midbody after anaphase onset and then slowly disappear, and ‘stable’ midbody proteins—including CIT-K, KIF14 and KIF23—which instead persist at the midbody throughout cytokinesis and also post abscission. These two classes of midbody proteins display distinct interaction networks with ubiquitylation factors, which could potentially explain their different dynamics and stability during cytokinesis. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis II)
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Review

Jump to: Research

35 pages, 2051 KiB  
Review
Lipid Polarization during Cytokinesis
by Govind Kunduri, Usha Acharya and Jairaj K. Acharya
Cells 2022, 11(24), 3977; https://doi.org/10.3390/cells11243977 - 08 Dec 2022
Cited by 2 | Viewed by 4269
Abstract
The plasma membrane of eukaryotic cells is composed of a large number of lipid species that are laterally segregated into functional domains as well as asymmetrically distributed between the outer and inner leaflets. Additionally, the spatial distribution and organization of these lipids dramatically [...] Read more.
The plasma membrane of eukaryotic cells is composed of a large number of lipid species that are laterally segregated into functional domains as well as asymmetrically distributed between the outer and inner leaflets. Additionally, the spatial distribution and organization of these lipids dramatically change in response to various cellular states, such as cell division, differentiation, and apoptosis. Division of one cell into two daughter cells is one of the most fundamental requirements for the sustenance of growth in all living organisms. The successful completion of cytokinesis, the final stage of cell division, is critically dependent on the spatial distribution and organization of specific lipids. In this review, we discuss the properties of various lipid species associated with cytokinesis and the mechanisms involved in their polarization, including forward trafficking, endocytic recycling, local synthesis, and cortical flow models. The differences in lipid species requirements and distribution in mitotic vs. male meiotic cells will be discussed. We will concentrate on sphingolipids and phosphatidylinositols because their transbilayer organization and movement may be linked via the cytoskeleton and thus critically regulate various steps of cytokinesis. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis II)
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23 pages, 1464 KiB  
Review
Minor Kinases with Major Roles in Cytokinesis Regulation
by Stefano Sechi, Roberto Piergentili and Maria Grazia Giansanti
Cells 2022, 11(22), 3639; https://doi.org/10.3390/cells11223639 - 17 Nov 2022
Cited by 3 | Viewed by 3605
Abstract
Cytokinesis, the conclusive act of cell division, allows cytoplasmic organelles and chromosomes to be faithfully partitioned between two daughter cells. In animal organisms, its accurate regulation is a fundamental task for normal development and for preventing aneuploidy. Cytokinesis failures produce genetically unstable tetraploid [...] Read more.
Cytokinesis, the conclusive act of cell division, allows cytoplasmic organelles and chromosomes to be faithfully partitioned between two daughter cells. In animal organisms, its accurate regulation is a fundamental task for normal development and for preventing aneuploidy. Cytokinesis failures produce genetically unstable tetraploid cells and ultimately result in chromosome instability, a hallmark of cancer cells. In animal cells, the assembly and constriction of an actomyosin ring drive cleavage furrow ingression, resulting in the formation of a cytoplasmic intercellular bridge, which is severed during abscission, the final event of cytokinesis. Kinase-mediated phosphorylation is a crucial process to orchestrate the spatio-temporal regulation of the different stages of cytokinesis. Several kinases have been described in the literature, such as cyclin-dependent kinase, polo-like kinase 1, and Aurora B, regulating both furrow ingression and/or abscission. However, others exist, with well-established roles in cell-cycle progression but whose specific role in cytokinesis has been poorly investigated, leading to considering these kinases as “minor” actors in this process. Yet, they deserve additional attention, as they might disclose unexpected routes of cell division regulation. Here, we summarize the role of multifunctional kinases in cytokinesis with a special focus on those with a still scarcely defined function during cell cleavage. Moreover, we discuss their implication in cancer. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis II)
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12 pages, 1156 KiB  
Review
Phase Separation in the Nucleus and at the Nuclear Periphery during Post-Mitotic Nuclear Envelope Reformation
by Klizia Maccaroni, Mattia La Torre, Romina Burla and Isabella Saggio
Cells 2022, 11(11), 1749; https://doi.org/10.3390/cells11111749 - 25 May 2022
Cited by 2 | Viewed by 3226
Abstract
Membrane-enclosed organelle compartmentalization is not the only way by which cell processes are spatially organized. Phase separation is emerging as a new driver in the organization of membrane-less compartments and biological processes. Liquid–liquid phase separation has been indicated as a new way to [...] Read more.
Membrane-enclosed organelle compartmentalization is not the only way by which cell processes are spatially organized. Phase separation is emerging as a new driver in the organization of membrane-less compartments and biological processes. Liquid–liquid phase separation has been indicated as a new way to control the kinetics of molecular reactions and is based on weak multivalent interactions affecting the stoichiometry of the molecules involved. In the nucleus, liquid–liquid phase separation may represent an ancestral means of controlling genomic activity by forming discrete chromatin regions, regulating transcriptional activity, contributing to the assembly of DNA damage response foci, and controlling the organization of chromosomes. Liquid–liquid phase separation also contributes to chromatin function through its role in the reorganization of the nuclear periphery in the post-mitotic phase. Herein, we describe the basic principles regulating liquid–liquid phase separation, analyze examples of phase separation occurring in the nucleus, and dedicate attention to the implication of liquid–liquid phase separation in the reorganization of the nuclear periphery by the endosomal sorting complexes required for transport (ESCRT) machinery. Although some caution is warranted, current scientific knowledge allows for the hypothesis that many factors and processes in the cell are yet to be discovered which are functionally associated with phase separation. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis II)
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