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  1. Article ; Online: Mechanobiology of the nucleus during the G2-M transition.

    Lima, Joana T / Ferreira, Jorge G

    Nucleus (Austin, Tex.)

    2024  Volume 15, Issue 1, Page(s) 2330947

    Abstract: Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged ... ...

    Abstract Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.
    MeSH term(s) Mechanotransduction, Cellular ; Cell Nucleus/metabolism ; Mitosis ; Cytoskeleton/metabolism ; Biophysics
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2619626-8
    ISSN 1949-1042 ; 1949-1042
    ISSN (online) 1949-1042
    ISSN 1949-1042
    DOI 10.1080/19491034.2024.2330947
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The LINC complex ensures accurate centrosome positioning during prophase.

    Lima, Joana T / Pereira, António J / Ferreira, Jorge G

    Life science alliance

    2024  Volume 7, Issue 4

    Abstract: Accurate centrosome separation and positioning during early mitosis relies on force-generating mechanisms regulated by a combination of extracellular, cytoplasmic, and nuclear cues. The identity of the nuclear cues involved in this process remains ... ...

    Abstract Accurate centrosome separation and positioning during early mitosis relies on force-generating mechanisms regulated by a combination of extracellular, cytoplasmic, and nuclear cues. The identity of the nuclear cues involved in this process remains largely unknown. Here, we investigate how the prophase nucleus contributes to centrosome positioning during the initial stages of mitosis, using a combination of cell micropatterning, high-resolution live-cell imaging, and quantitative 3D cellular reconstruction. We show that in untransformed RPE-1 cells, centrosome positioning is regulated by a nuclear signal, independently of external cues. This nuclear mechanism relies on the linker of nucleoskeleton and cytoskeleton complex that controls the timely loading of dynein on the nuclear envelope (NE), providing spatial cues for robust centrosome positioning on the shortest nuclear axis, before nuclear envelope permeabilization. Our results demonstrate how nuclear-cytoskeletal coupling maintains a robust centrosome positioning mechanism to ensure efficient mitotic spindle assembly.
    MeSH term(s) Nuclear Envelope ; Centrosome ; Mitosis ; Prophase ; Cell Nucleus
    Language English
    Publishing date 2024-01-16
    Publishing country United States
    Document type Journal Article
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202302404
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Nucleus-Cytoskeleton Crosstalk During Mitotic Entry.

    Dantas, Margarida / Lima, Joana T / Ferreira, Jorge G

    Frontiers in cell and developmental biology

    2021  Volume 9, Page(s) 649899

    Abstract: In preparation for mitosis, cells undergo extensive reorganization of the cytoskeleton and nucleus, so that chromosomes can be efficiently segregated into two daughter cells. Coordination of these cytoskeletal and nuclear events occurs through ... ...

    Abstract In preparation for mitosis, cells undergo extensive reorganization of the cytoskeleton and nucleus, so that chromosomes can be efficiently segregated into two daughter cells. Coordination of these cytoskeletal and nuclear events occurs through biochemical regulatory pathways, orchestrated by Cyclin-CDK activity. However, recent studies provide evidence that physical forces are also involved in the early steps of spindle assembly. Here, we will review how the crosstalk of physical forces and biochemical signals coordinates nuclear and cytoplasmic events during the G2-M transition, to ensure efficient spindle assembly and faithful chromosome segregation.
    Language English
    Publishing date 2021-03-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2021.649899
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: High-Resolution Analysis of Centrosome Behavior During Mitosis.

    Nunes, Vanessa / Dantas, Margarida / Lima, Joana T / Ferreira, Jorge G

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2329, Page(s) 179–194

    Abstract: Cell division requires a dynamic reorganization of cytoskeletal and nuclear components. One essential step is the separation of centrosomes, which allows the assembly of a microtubule-based mitotic spindle. This has to be spatially and temporally ... ...

    Abstract Cell division requires a dynamic reorganization of cytoskeletal and nuclear components. One essential step is the separation of centrosomes, which allows the assembly of a microtubule-based mitotic spindle. This has to be spatially and temporally coordinated with other events such as adhesion complex disengagement, assembly of an actin-rich cell cortex and nuclear envelope breakdown (NEB), to ensure chromosome segregation fidelity. Previous methodologies often focused on a single event and failed to provide an integrated view of the process. In this chapter, we describe a method to study mitosis with high resolution, by analyzing the dynamic interplay between centrosomes, nucleus, and cell membrane, using a combination of live-cell imaging and micromanipulation with custom-designed computational tools.
    MeSH term(s) Cell Line ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; Centrosome/metabolism ; Chromosome Segregation ; Computational Biology ; HeLa Cells ; Humans ; Mitosis ; Time-Lapse Imaging/methods
    Language English
    Publishing date 2021-06-03
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1538-6_13
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  5. Article ; Online: Trackosome: a computational toolbox to study the spatiotemporal dynamics of centrosomes, nuclear envelope and cellular membrane.

    Castro, Domingos / Nunes, Vanessa / Lima, Joana T / Ferreira, Jorge G / Aguiar, Paulo

    Journal of cell science

    2020  Volume 133, Issue 24

    Abstract: During the initial stages of mitosis, multiple mechanisms drive centrosome separation and positioning. How they are coordinated to promote centrosome migration to opposite sides of the nucleus remains unclear. Here, we present Trackosome, an open-source ... ...

    Abstract During the initial stages of mitosis, multiple mechanisms drive centrosome separation and positioning. How they are coordinated to promote centrosome migration to opposite sides of the nucleus remains unclear. Here, we present Trackosome, an open-source image analysis software for tracking centrosomes and reconstructing nuclear and cellular membranes, based on volumetric live-imaging data. The toolbox runs in MATLAB and provides a graphical user interface for easy access to the tracking and analysis algorithms. It provides detailed quantification of the spatiotemporal relationships between centrosomes, nuclear envelope and cellular membrane, and can also be used to measure the dynamic fluctuations of the nuclear envelope. These fluctuations are important because they are related to the mechanical forces exerted on the nucleus by its adjacent cytoskeletal structures. Unlike previous algorithms based on circular or elliptical approximations, Trackosome measures membrane movement in a model-free condition, making it viable for irregularly shaped nuclei. Using Trackosome, we demonstrate significant correlations between the movements of the centrosomes, and identify specific oscillation modes of the nuclear envelope. Overall, Trackosome is a powerful tool that can be used to help unravel new elements in the spatiotemporal dynamics of subcellular structures.
    MeSH term(s) Cell Nucleus ; Centrosome ; Mitosis ; Nuclear Envelope ; Spindle Apparatus
    Language English
    Publishing date 2020-12-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.252254
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1200: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  6. Article ; Online: α-Tubulin detyrosination impairs mitotic error correction by suppressing MCAK centromeric activity.

    Ferreira, Luísa T / Orr, Bernardo / Rajendraprasad, Girish / Pereira, António J / Lemos, Carolina / Lima, Joana T / Guasch Boldú, Clàudia / Ferreira, Jorge G / Barisic, Marin / Maiato, Helder

    The Journal of cell biology

    2020  Volume 219, Issue 4

    Abstract: Incorrect kinetochore-microtubule attachments during mitosis can lead to chromosomal instability, a hallmark of human cancers. Mitotic error correction relies on the kinesin-13 MCAK, a microtubule depolymerase whose activity in vitro is suppressed by α- ... ...

    Abstract Incorrect kinetochore-microtubule attachments during mitosis can lead to chromosomal instability, a hallmark of human cancers. Mitotic error correction relies on the kinesin-13 MCAK, a microtubule depolymerase whose activity in vitro is suppressed by α-tubulin detyrosination-a posttranslational modification enriched on long-lived microtubules. However, whether and how MCAK activity required for mitotic error correction is regulated by α-tubulin detyrosination remains unknown. Here we found that detyrosinated α-tubulin accumulates on correct, more stable, kinetochore-microtubule attachments. Experimental manipulation of tubulin tyrosine ligase (TTL) or carboxypeptidase (Vasohibins-SVBP) activities to constitutively increase α-tubulin detyrosination near kinetochores compromised efficient error correction, without affecting overall kinetochore microtubule stability. Rescue experiments indicate that MCAK centromeric activity was required and sufficient to correct the mitotic errors caused by excessive α-tubulin detyrosination independently of its global impact on microtubule dynamics. Thus, microtubules are not just passive elements during mitotic error correction, and the extent of α-tubulin detyrosination allows centromeric MCAK to discriminate correct vs. incorrect kinetochore-microtubule attachments, thereby promoting mitotic fidelity.
    MeSH term(s) Cell Line, Tumor ; Centromere/metabolism ; Humans ; Kinesin/metabolism ; Microtubules/metabolism ; Mitosis ; Tubulin/metabolism
    Chemical Substances KIF2C protein, human ; Tubulin ; Kinesin (EC 3.6.4.4)
    Language English
    Publishing date 2020-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.201910064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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