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

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

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 27050

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. This Special Issue will increase our knowledge of an intricate process, requiring at least one hundred proteins and a tight coordination between actin and microtubule cytoskeletal components and membrane trafficking regulators. 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 develop new therapeutic strategies for cancer and other diseases.

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 (6 papers)

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Research

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17 pages, 3449 KiB  
Article
Extrachromosomal Histone H2B Contributes to the Formation of the Abscission Site for Cell Division
by Laura Monteonofrio, Davide Valente, Cinzia Rinaldo and Silvia Soddu
Cells 2019, 8(11), 1391; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8111391 - 05 Nov 2019
Cited by 5 | Viewed by 3277
Abstract
Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that [...] Read more.
Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that ecH2B binds and colocalizes with CHMP4B, a key component of the ESCRT-III machinery responsible for abscission, the final step of cell division. Abscission requires the formation of an abscission site at the ICB where the ESCRT-III complex organizes into narrowing cortical helices that drive the physical separation of sibling cells. ecH2B depletion does not prevent membrane cleavage rather results in abscission delay and accumulation of abnormally long and thin ICBs. In the absence of ecH2B, CHMP4B and other components of the fission machinery, such as IST1 and Spastin, are recruited to the ICB and localize at the midbody. However, in the late stage of abscission, these fission factors fail to re-localize at the periphery of the midbody and the abscission site fails to form. These results show that extrachromosomal activity of histone H2B is required in the formation of the abscission site and the proper localization of the fission machinery. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis)
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18 pages, 5054 KiB  
Article
Dynamin-Like Protein B of Dictyostelium Contributes to Cytokinesis Cooperatively with Other Dynamins
by Koushiro Fujimoto, Masahito Tanaka, A.Y. K. Md. Masud Rana, Md. Golam Sarowar Jahan, Go Itoh, Masatsune Tsujioka, Taro Q. P. Uyeda, Shin-ya Miyagishima and Shigehiko Yumura
Cells 2019, 8(8), 781; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080781 - 26 Jul 2019
Cited by 9 | Viewed by 3815
Abstract
Dynamin is a large GTPase responsible for diverse cellular processes, such as endocytosis, division of organelles, and cytokinesis. The social amoebozoan, Dictyostelium discoideum, has five dynamin-like proteins: dymA, dymB, dlpA, dlpB, and dlpC. DymA, dlpA, or dlpB-deficient cells exhibited defects in cytokinesis. [...] Read more.
Dynamin is a large GTPase responsible for diverse cellular processes, such as endocytosis, division of organelles, and cytokinesis. The social amoebozoan, Dictyostelium discoideum, has five dynamin-like proteins: dymA, dymB, dlpA, dlpB, and dlpC. DymA, dlpA, or dlpB-deficient cells exhibited defects in cytokinesis. DlpA and dlpB were found to colocalize at cleavage furrows from the early phase, and dymA localized at the intercellular bridge connecting the two daughter cells, indicating that these dynamins contribute to cytokinesis at distinct dividing stages. Total internal reflection fluorescence microscopy revealed that dlpA and dlpB colocalized at individual dots at the furrow cortex. However, dlpA and dlpB did not colocalize with clathrin, suggesting that they are not involved in clathrin-mediated endocytosis. The fact that dlpA did not localize at the furrow in dlpB null cells and vice versa, as well as other several lines of evidence, suggests that hetero-oligomerization of dlpA and dlpB is required for them to bind to the furrow. The hetero-oligomers directly or indirectly associate with actin filaments, stabilizing them in the contractile rings. Interestingly, dlpA, but not dlpB, accumulated at the phagocytic cups independently of dlpB. Our results suggest that the hetero-oligomers of dlpA and dlpB contribute to cytokinesis cooperatively with dymA. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis)
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12 pages, 2305 KiB  
Article
HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission
by Alessandra Pisciottani, Loredana Biancolillo, Manuela Ferrara, Davide Valente, Francesca Sardina, Laura Monteonofrio, Serena Camerini, Marco Crescenzi, Silvia Soddu and Cinzia Rinaldo
Cells 2019, 8(7), 684; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8070684 - 05 Jul 2019
Cited by 20 | Viewed by 4118
Abstract
Abscission is the final step of cell division, mediating the physical separation of the two daughter cells. A key player in this process is the microtubule-severing enzyme spastin that localizes at the midbody where its activity is crucial to cut microtubules and culminate [...] Read more.
Abscission is the final step of cell division, mediating the physical separation of the two daughter cells. A key player in this process is the microtubule-severing enzyme spastin that localizes at the midbody where its activity is crucial to cut microtubules and culminate the cytokinesis. Recently, we demonstrated that HIPK2, a multifunctional kinase involved in several cellular pathways, contributes to abscission and prevents tetraploidization. Here, we show that HIPK2 binds and phosphorylates spastin at serine 268. During cytokinesis, the midbody-localized spastin is phosphorylated at S268 in HIPK2-proficient cells. In contrast, no spastin is detectable at the midbody in HIPK2-depleted cells. The non-phosphorylatable spastin-S268A mutant does not localize at the midbody and cannot rescue HIPK2-depleted cells from abscission defects. In contrast, the phosphomimetic spastin-S268D mutant localizes at the midbody and restores successful abscission in the HIPK2-depleted cells. These results show that spastin is a novel target of HIPK2 and that HIPK2-mediated phosphorylation of spastin contributes to its midbody localization for successful abscission. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis)
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11 pages, 4062 KiB  
Article
Cytokinesis D is Mediated by Cortical Flow of Dividing Cells Instead of Chemotaxis
by Yuki Tanaka, Md. Golam Sarowar Jahan, Tomo Kondo, Masaki Nakano and Shigehiko Yumura
Cells 2019, 8(5), 473; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8050473 - 17 May 2019
Cited by 10 | Viewed by 3579
Abstract
Cytokinesis D is known as the midwife mechanism in which neighboring cells facilitate cell division by crossing the cleavage furrow of dividing cells. Cytokinesis D is thought to be mediated by chemotaxis, where midwife cells migrate toward dividing cells by sensing an unknown [...] Read more.
Cytokinesis D is known as the midwife mechanism in which neighboring cells facilitate cell division by crossing the cleavage furrow of dividing cells. Cytokinesis D is thought to be mediated by chemotaxis, where midwife cells migrate toward dividing cells by sensing an unknown chemoattractant secreted from the cleavage furrow. In this study, to validate this chemotaxis model, we aspirated the fluid from the vicinity of the cleavage furrow of a dividing Dictyostelium cell and discharged it onto a neighboring cell using a microcapillary. However, the neighboring cells did not show any chemotaxis toward the fluid. In addition, the cells did not manifest an increase in the levels of intracellular Ca2+, cAMP, or cGMP, which are expected to rise in chemotaxing cells. From several lines of our experiments, including these findings, we concluded that chemotaxis does not contribute to cytokinesis D. As an alternative, we propose a cortical-flow model, where a migrating cell attaches to a dividing cell by chance and is guided toward the furrow by the cortical flow on the dividing cell, and then physically assists the separation of the daughter cells. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis)
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Review

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17 pages, 2226 KiB  
Review
Cytokinesis in Eukaryotic Cells: The Furrow Complexity at a Glance
by Roberta Fraschini
Cells 2020, 9(2), 271; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9020271 - 22 Jan 2020
Cited by 16 | Viewed by 6886
Abstract
The duplication cycle is the fascinating process that, starting from a cell, results in the formation of two daughter cells and it is essential for life. Cytokinesis is the final step of the cell cycle, it is a very complex phase, and is [...] Read more.
The duplication cycle is the fascinating process that, starting from a cell, results in the formation of two daughter cells and it is essential for life. Cytokinesis is the final step of the cell cycle, it is a very complex phase, and is a concert of forces, remodeling, trafficking, and cell signaling. All of the steps of cell division must be properly coordinated with each other to faithfully segregate the genetic material and this task is fundamental for generating viable cells. Given the importance of this process, molecular pathways and proteins that are involved in cytokinesis are conserved from yeast to humans. In this review, we describe symmetric and asymmetric cell division in animal cell and in a model organism, budding yeast. In addition, we illustrate the surveillance mechanisms that ensure a proper cell division and discuss the connections with normal cell proliferation and organs development and with the occurrence of human diseases. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis)
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15 pages, 4271 KiB  
Review
The Cell Wall Hydrolytic NlpC/P60 Endopeptidases in Mycobacterial Cytokinesis: A Structural Perspective
by Flavia Squeglia, Miguel Moreira, Alessia Ruggiero and Rita Berisio
Cells 2019, 8(6), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8060609 - 18 Jun 2019
Cited by 13 | Viewed by 4548
Abstract
In preparation for division, bacteria replicate their DNA and segregate the newly formed chromosomes. A division septum then assembles between the chromosomes, and the mother cell splits into two identical daughters due to septum degradation. A major constituent of bacterial septa and of [...] Read more.
In preparation for division, bacteria replicate their DNA and segregate the newly formed chromosomes. A division septum then assembles between the chromosomes, and the mother cell splits into two identical daughters due to septum degradation. A major constituent of bacterial septa and of the whole cell wall is peptidoglycan (PGN), an essential cell wall polymer, formed by glycan chains of β−(1-4)-linked-N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), cross-linked by short peptide stems. Depending on the amino acid located at the third position of the peptide stem, PGN is classified as either Lys-type or meso-diaminopimelic acid (DAP)-type. Hydrolytic enzymes play a crucial role in the degradation of bacterial septa to split the cell wall material shared by adjacent daughter cells to promote their separation. In mycobacteria, a key PGN hydrolase, belonging to the NlpC/P60 endopeptidase family and denoted as RipA, is responsible for the degradation of septa, as the deletion of the gene encoding for this enzyme generates abnormal bacteria with multiple septa. This review provides an update of structural and functional data highlighting the central role of RipA in mycobacterial cytokinesis and the fine regulation of its catalytic activity, which involves multiple molecular partners. Full article
(This article belongs to the Special Issue Molecular Factors and Mechanisms Involved in Cytokinesis)
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