Special Issue "Cytoskeleton and Regulation of Mitosis"

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (30 November 2018)

Special Issue Editors

Guest Editor
Dr. Marin Barisic

1) Danish Cancer Society Research Center, Copenhagen, Denmark; 2) Faculty of Health Sciences, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
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Interests: Mitosis; Microtubule dynamics; Tubulin posttranslational modifications; Motor proteins; Kinetochores; Chromosome movements in mitosis; Cell migration
Guest Editor
Dr. Jorge Ferreira

1) Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal; 2) Department of Biomedicine, Faculty of Medicine – University of Porto, Porto, Portugal
Website | E-Mail
Interests: Mitosis; Cytoskeleton; Centrosomes; Mechanobiology; Cell shape; Chromosome segregation

Special Issue Information

Dear Colleagues,

Entry and progression through mitosis requires extensive reorganization of the cytoskeleton. These cytoskeletal changes need to be tightly coupled with the main mitotic regulators to ensure that cells assemble a functional mitotic spindle, capture and correctly segregate chromosomes and finally, complete cytokinesis.

In this Special Issue, we invite colleagues to submit both their original research articles and reviews on the crosstalk between cytoskeleton and mitosis. Topics of interest include, but are not limited to, microtubule dynamics, mitotic spindle assembly and disassembly, motor-proteins driven processes, chromosome motion, kinetochore–microtubule interface, kinases and phosphatases-based regulation, technology and methods for investigation and analysis of cytoskeleton and cell division. Bringing together the current work and views on cytoskeleton and regulation of mitosis, we aim to boost further exploration and better understanding of the processes that ensure faithful cell division.

Dr. Marin Barisic
Dr. Jorge Ferreira
Guest Editors

Manuscript Submission Information

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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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • Cytoskeleton
  • Chromosome segregation
  • Mitosis
  • Chromosomal Instability
  • Molecular motors

Published Papers (11 papers)

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Research

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Open AccessArticle
Tubulin Acetylation Mediates Bisphenol A Effects on the Microtubule Arrays of Allium cepa and Triticum turgidum
Biomolecules 2019, 9(5), 185; https://doi.org/10.3390/biom9050185
Received: 14 March 2019 / Revised: 29 April 2019 / Accepted: 6 May 2019 / Published: 11 May 2019
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Abstract
The effects of bisphenol A (BPA), a prevalent endocrine disruptor, on both interphase and mitotic microtubule array organization was examined by immunofluorescence microscopy in meristematic root cells of Triticum turgidum (durum wheat) and Allium cepa (onion). In interphase cells of A. cepa, [...] Read more.
The effects of bisphenol A (BPA), a prevalent endocrine disruptor, on both interphase and mitotic microtubule array organization was examined by immunofluorescence microscopy in meristematic root cells of Triticum turgidum (durum wheat) and Allium cepa (onion). In interphase cells of A. cepa, BPA treatment resulted in substitution of cortical microtubules by annular/spiral tubulin structures, while in T. turgidum BPA induced cortical microtubule fragmentation. Immunolocalization of acetylated α-tubulin revealed that cortical microtubules of T. turgidum were highly acetylated, unlike those of A. cepa. In addition, elevation of tubulin acetylation by trichostatin A in A. cepa resulted in microtubule disruption similar to that observed in T. turgidum. BPA also disrupted all mitotic microtubule arrays in both species. It is also worth noting that mitotic microtubule arrays were acetylated in both plants. As assessed by BPA removal, its effects are reversible. Furthermore, taxol-stabilized microtubules were resistant to BPA, while recovery from oryzalin treatment in BPA solution resulted in the formation of ring-like tubulin conformations. Overall, these findings indicate the following: (1) BPA affects plant mitosis/cytokinesis by disrupting microtubule organization. (2) Microtubule disassembly probably results from impairment of free tubulin subunit polymerization. (3) The differences in cortical microtubule responses to BPA among the species studied are correlated to the degree of tubulin acetylation. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessArticle
Quantifying Tubulin Concentration and Microtubule Number Throughout the Fission Yeast Cell Cycle
Biomolecules 2019, 9(3), 86; https://doi.org/10.3390/biom9030086
Received: 19 December 2018 / Revised: 25 February 2019 / Accepted: 26 February 2019 / Published: 4 March 2019
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Abstract
The fission yeast Schizosaccharomyces pombe serves as a good genetic model organism for the molecular dissection of the microtubule (MT) cytoskeleton. However, analysis of the number and distribution of individual MTs throughout the cell cycle, particularly during mitosis, in living cells is still [...] Read more.
The fission yeast Schizosaccharomyces pombe serves as a good genetic model organism for the molecular dissection of the microtubule (MT) cytoskeleton. However, analysis of the number and distribution of individual MTs throughout the cell cycle, particularly during mitosis, in living cells is still lacking, making quantitative modelling imprecise. We use quantitative fluorescent imaging and analysis to measure the changes in tubulin concentration and MT number and distribution throughout the cell cycle at a single MT resolution in living cells. In the wild-type cell, both mother and daughter spindle pole body (SPB) nucleate a maximum of 23 ± 6 MTs at the onset of mitosis, which decreases to a minimum of 4 ± 1 MTs at spindle break down. Interphase MT bundles, astral MT bundles, and the post anaphase array (PAA) microtubules are composed primarily of 1 ± 1 individual MT along their lengths. We measure the cellular concentration of αβ-tubulin subunits to be ~5 µM throughout the cell cycle, of which one-third is in polymer form during interphase and one-quarter is in polymer form during mitosis. This analysis provides a definitive characterization of αβ-tubulin concentration and MT number and distribution in fission yeast and establishes a foundation for future quantitative comparison of mutants defective in MTs. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessArticle
Light-Induced Protein Clustering for Optogenetic Interference and Protein Interaction Analysis in Drosophila S2 Cells
Biomolecules 2019, 9(2), 61; https://doi.org/10.3390/biom9020061
Received: 11 December 2018 / Revised: 30 January 2019 / Accepted: 30 January 2019 / Published: 12 February 2019
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Abstract
Drosophila Schneider 2 (S2) cells are a simple and powerful system commonly used in cell biology because they are well suited for high resolution microscopy and RNAi-mediated depletion. However, understanding dynamic processes, such as cell division, also requires methodology to interfere with protein [...] Read more.
Drosophila Schneider 2 (S2) cells are a simple and powerful system commonly used in cell biology because they are well suited for high resolution microscopy and RNAi-mediated depletion. However, understanding dynamic processes, such as cell division, also requires methodology to interfere with protein function with high spatiotemporal control. In this research study, we report the adaptation of an optogenetic tool to Drosophila S2 cells. Light-activated reversible inhibition by assembled trap (LARIAT) relies on the rapid light-dependent heterodimerization between cryptochrome 2 (CRY2) and cryptochrome-interacting bHLH 1 (CIB1) to form large protein clusters. An anti-green fluorescent protein (GFP) nanobody fused with CRY2 allows this method to quickly trap any GFP-tagged protein in these light-induced protein clusters. We evaluated clustering kinetics in response to light for different LARIAT modules, and showed the ability of GFP-LARIAT to inactivate the mitotic protein Mps1 and to disrupt the membrane localization of the polarity regulator Lethal Giant Larvae (Lgl). Moreover, we validated light-induced co-clustering assays to assess protein-protein interactions in S2 cells. In conclusion, GFP-based LARIAT is a versatile tool to answer different biological questions, since it enables probing of dynamic processes and protein-protein interactions with high spatiotemporal resolution in Drosophila S2 cells. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessArticle
Impaired CENP-E Function Renders Large Chromosomes More Vulnerable to Congression Failure
Biomolecules 2019, 9(2), 44; https://doi.org/10.3390/biom9020044
Received: 19 December 2018 / Revised: 18 January 2019 / Accepted: 21 January 2019 / Published: 26 January 2019
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Abstract
It has recently emerged that human chromosomes vary between one another in terms of features that impact their behaviour during impaired chromosome segregation, leading to non-random aneuploidy in the daughter cell population. During the process of chromosome congression to the metaphase plate, chromosome [...] Read more.
It has recently emerged that human chromosomes vary between one another in terms of features that impact their behaviour during impaired chromosome segregation, leading to non-random aneuploidy in the daughter cell population. During the process of chromosome congression to the metaphase plate, chromosome movement is guided by kinesin-like proteins, among which centromere-associated protein E (CENP-E) is important to transport chromosomes along the microtubules of the mitotic spindle. It is known that the inhibition of CENP-E notably impairs alignment for a subset of chromosomes, particularly those positioned close to the centrosome at nuclear envelope breakdown (‘polar chromosomes’); it is, however, not clear whether chromosome identity could influence this process. Since a popular strategy to model aneuploidy is to induce congression defects (for example combining CENP-E inhibitors with mitotic checkpoint abrogation), variance in congression efficiency between chromosomes might influence the landscape of aneuploidy and subsequent cell fates. By combining immunofluorescence, live cell imaging and fluorescence in situ hybridisation, we investigated the behaviour of polar chromosomes and their dependency upon CENP-E-mediated congression in human cells. We observed a bias in congression efficiency related to chromosome size, with larger chromosomes more sensitive to CENP-E inhibition. This bias is likely due to two contributing factors; an initial propensity of larger chromosomes to be peripheral and thus rely more upon CENP-E function to migrate to the metaphase plate, and additionally a bias between specific chromosomes’ ability to congress from a polar state. These findings may help to explain the persistence of a subset of chromosomes at the centrosome following CENP-E disruption, and also have implications for the spectrum of aneuploidy generated following treatments to manipulate CENP-E function. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessFeature PaperArticle
Delayed Chromosome Alignment to the Spindle Equator Increases the Rate of Chromosome Missegregation in Cancer Cell Lines
Biomolecules 2019, 9(1), 10; https://doi.org/10.3390/biom9010010
Received: 27 November 2018 / Revised: 20 December 2018 / Accepted: 21 December 2018 / Published: 28 December 2018
Cited by 2 | PDF Full-text (4598 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
For appropriate chromosome segregation, kinetochores on sister chromatids have to attach to microtubules from opposite spindle poles (bi-orientation). Chromosome alignment at the spindle equator, referred to as congression, can occur through the attachment of kinetochores to the lateral surface of spindle microtubules, facilitating [...] Read more.
For appropriate chromosome segregation, kinetochores on sister chromatids have to attach to microtubules from opposite spindle poles (bi-orientation). Chromosome alignment at the spindle equator, referred to as congression, can occur through the attachment of kinetochores to the lateral surface of spindle microtubules, facilitating bi-orientation establishment. However, the contribution of this phenomenon to mitotic fidelity has not been clarified yet. Here, we addressed whether delayed chromosome alignment to the spindle equator increases the rate of chromosome missegregation. Cancer cell lines depleted of Kid, a chromokinesin involved in chromosome congression, showed chromosome alignment with a slight delay, and increased frequency of lagging chromosomes. Delayed chromosome alignment concomitant with an increased rate of lagging chromosomes was also seen in cells depleted of kinesin family member 4A (KIF4A), another chromokinesin. Cells that underwent chromosome missegregation took relatively longer time to align chromosomes in both control and Kid/KIF4A-depleted cells. Tracking of late-aligning chromosomes showed that they exhibit a higher rate of lagging chromosomes. Intriguingly, the metaphase of cells that underwent chromosome missegregation was shortened, and delaying anaphase onset ameliorated the increased chromosome missegregation. These data suggest that late-aligning chromosomes do not have sufficient time to establish bi-orientation, leading to chromosome missegregation. Our data imply that delayed chromosome alignment is not only a consequence, but also a cause of defective bi-orientation establishment, which can lead to chromosomal instability in cells without severe mitotic defects. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Review

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Open AccessReview
Network Contractility during Cytokinesis—From Molecular to Global Views
Biomolecules 2019, 9(5), 194; https://doi.org/10.3390/biom9050194
Received: 19 March 2019 / Revised: 30 April 2019 / Accepted: 30 April 2019 / Published: 18 May 2019
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Abstract
Cytokinesis is the last stage of cell division, which partitions the mother cell into two daughter cells. It requires the assembly and constriction of a contractile ring that consists of a filamentous contractile network of actin and myosin. Network contractility depends on network [...] Read more.
Cytokinesis is the last stage of cell division, which partitions the mother cell into two daughter cells. It requires the assembly and constriction of a contractile ring that consists of a filamentous contractile network of actin and myosin. Network contractility depends on network architecture, level of connectivity and myosin motor activity, but how exactly is the contractile ring network organized or interconnected and how much it depends on motor activity remains unclear. Moreover, the contractile ring is not an isolated entity; rather, it is integrated into the surrounding cortex. Therefore, the mechanical properties of the cell cortex and cortical behaviors are expected to impact contractile ring functioning. Due to the complexity of the process, experimental approaches have been coupled to theoretical modeling in order to advance its global understanding. While earlier coarse-grained descriptions attempted to provide an integrated view of the process, recent models have mostly focused on understanding the behavior of an isolated contractile ring. Here we provide an overview of the organization and dynamics of the actomyosin network during cytokinesis and discuss existing theoretical models in light of cortical behaviors and experimental evidence from several systems. Our view on what is missing in current models and should be tested in the future is provided. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessReview
Helical Twist and Rotational Forces in the Mitotic Spindle
Biomolecules 2019, 9(4), 132; https://doi.org/10.3390/biom9040132
Received: 29 January 2019 / Revised: 24 March 2019 / Accepted: 28 March 2019 / Published: 1 April 2019
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Abstract
The mitotic spindle segregates chromosomes into two daughter cells during cell division. This process relies on the precise regulation of forces acting on chromosomes as the cell progresses through mitosis. The forces in the spindle are difficult to directly measure using the available [...] Read more.
The mitotic spindle segregates chromosomes into two daughter cells during cell division. This process relies on the precise regulation of forces acting on chromosomes as the cell progresses through mitosis. The forces in the spindle are difficult to directly measure using the available experimental techniques. Here, we review the ideas and recent advances of how forces can be determined from the spindle shape. By using these approaches, it has been shown that tension and compression coexist along a single kinetochore fiber, which are balanced by a bridging fiber between sister kinetochore fibers. An extension of this approach to three dimensions revealed that microtubule bundles have rich shapes, and extend not simply like meridians on the Earth’s surface but, rather, twisted in a helical manner. Such complex shapes are due to rotational forces, which, in addition to linear forces, act in the spindle and may be generated by motor proteins such as kinesin-5. These findings open new questions for future studies, to understand the mechanisms of rotational forces and reveal their biological roles in cells. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessReview
Mechanisms of Spindle Positioning: Lessons from Worms and Mammalian Cells
Biomolecules 2019, 9(2), 80; https://doi.org/10.3390/biom9020080
Received: 8 January 2019 / Revised: 13 February 2019 / Accepted: 18 February 2019 / Published: 25 February 2019
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Abstract
Proper positioning of the mitotic spindle is fundamental for specifying the site for cleavage furrow, and thus regulates the appropriate sizes and accurate distribution of the cell fate determinants in the resulting daughter cells during development and in the stem cells. The past [...] Read more.
Proper positioning of the mitotic spindle is fundamental for specifying the site for cleavage furrow, and thus regulates the appropriate sizes and accurate distribution of the cell fate determinants in the resulting daughter cells during development and in the stem cells. The past couple of years have witnessed tremendous work accomplished in the area of spindle positioning, and this has led to the emergence of a working model unravelling in-depth mechanistic insight of the underlying process orchestrating spindle positioning. It is evident now that the correct positioning of the mitotic spindle is not only guided by the chemical cues (protein–protein interactions) but also influenced by the physical nature of the cellular environment. In metazoans, the key players that regulate proper spindle positioning are the actin-rich cell cortex and associated proteins, the ternary complex (Gα/GPR-1/2/LIN-5 in Caenorhabditis elegans, Gαi/Pins/Mud in Drosophila and Gαi1-3/LGN/NuMA in humans), minus-end-directed motor protein dynein and the cortical machinery containing myosin. In this review, I will mainly discuss how the abovementioned components precisely and spatiotemporally regulate spindle positioning by sensing the physicochemical environment for execution of flawless mitosis. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessReview
Phosphatases in Mitosis: Roles and Regulation
Biomolecules 2019, 9(2), 55; https://doi.org/10.3390/biom9020055
Received: 17 December 2018 / Revised: 31 January 2019 / Accepted: 1 February 2019 / Published: 7 February 2019
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Abstract
Mitosis requires extensive rearrangement of cellular architecture and of subcellular structures so that replicated chromosomes can bind correctly to spindle microtubules and segregate towards opposite poles. This process originates two new daughter nuclei with equal genetic content and relies on highly-dynamic and tightly [...] Read more.
Mitosis requires extensive rearrangement of cellular architecture and of subcellular structures so that replicated chromosomes can bind correctly to spindle microtubules and segregate towards opposite poles. This process originates two new daughter nuclei with equal genetic content and relies on highly-dynamic and tightly regulated phosphorylation of numerous cell cycle proteins. A burst in protein phosphorylation orchestrated by several conserved kinases occurs as cells go into and progress through mitosis. The opposing dephosphorylation events are catalyzed by a small set of protein phosphatases, whose importance for the accuracy of mitosis is becoming increasingly appreciated. This review will focus on the established and emerging roles of mitotic phosphatases, describe their structural and biochemical properties, and discuss recent advances in understanding the regulation of phosphatase activity and function. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessReview
Aurora A Protein Kinase: To the Centrosome and Beyond
Biomolecules 2019, 9(1), 28; https://doi.org/10.3390/biom9010028
Received: 7 December 2018 / Revised: 9 January 2019 / Accepted: 9 January 2019 / Published: 15 January 2019
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Abstract
Accurate chromosome segregation requires the perfect spatiotemporal rearrangement of the cellular cytoskeleton. Isolated more than two decades ago from Drosophila, Aurora A is a widespread protein kinase that plays key roles during cell division. Numerous studies have described the localisation of Aurora [...] Read more.
Accurate chromosome segregation requires the perfect spatiotemporal rearrangement of the cellular cytoskeleton. Isolated more than two decades ago from Drosophila, Aurora A is a widespread protein kinase that plays key roles during cell division. Numerous studies have described the localisation of Aurora A at centrosomes, the mitotic spindle, and, more recently, at mitotic centromeres. In this review, we will summarise the cytoskeletal rearrangements regulated by Aurora A during cell division. We will also discuss the recent discoveries showing that Aurora A also controls not only the dynamics of the cortical proteins but also regulates the centromeric proteins, revealing new roles for this kinase during cell division. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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Open AccessReview
Emerging Insights into the Function of Kinesin-8 Proteins in Microtubule Length Regulation
Biomolecules 2019, 9(1), 1; https://doi.org/10.3390/biom9010001
Received: 29 November 2018 / Revised: 15 December 2018 / Accepted: 17 December 2018 / Published: 20 December 2018
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Abstract
Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the [...] Read more.
Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization. Full article
(This article belongs to the Special Issue Cytoskeleton and Regulation of Mitosis)
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