Prophase-Specific Perinuclear Actin Coordinates Centrosome Separation and Positioning to Ensure Accurate Chromosome Segregation

Stiff, Tom; Iturra, Fabio Echegaray; Pink, Harry; Herbert, Alex; Reyes-Aldasoro, Constantino Carlos; Hochegger, Helfrid

doi:10.1016/j.celrep.2020.107681

Cited by 28 publications

(33 citation statements)

References 73 publications

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“…Similarly, in cultured human cells, depletion of both SUN1 and SUN2 delayed NE disassembly (Figure 2), similarly to what is observed after microtubule depolymerization with nocodazole (Turgay et al, 2014). Consequently, centrosome separation is disrupted (Stiff et al, 2020) and mitotic progression affected (Turgay et al, 2014). Moreover, an intact LINC complex is essential during early mitosis for decreasing chromosome scattering (Booth et al, 2019), likely facilitating their capture and congression (Booth et al, 2019;Stiff et al, 2020).…”

Section: The Nucleus and Nucleo-cytoskeletal Couplingsupporting

confidence: 64%

“…Consequently, centrosome separation is disrupted ( Stiff et al, 2020 ) and mitotic progression affected ( Turgay et al, 2014 ). Moreover, an intact LINC complex is essential during early mitosis for decreasing chromosome scattering ( Booth et al, 2019 ), likely facilitating their capture and congression ( Booth et al, 2019 ; Stiff et al, 2020 ). Importantly, the LINC complex also directly associates with dynein on the NE to control nuclear migration ( Malone et al, 2003 ; Zhang et al, 2009 ; Fridolfsson and Starr, 2010 ; Yu et al, 2011 ) and meiotic chromosome movement ( Chikashige et al, 2006 ; Sato et al, 2009 ).…”

Section: The Nucleus and Nucleo-cytoskeletal Couplingmentioning

confidence: 99%

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Nucleus-Cytoskeleton Crosstalk During Mitotic Entry

Dantas

Lima

Ferreira

2021

Front. Cell Dev. Biol.

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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.

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Section: The Nucleus and Nucleo-cytoskeletal Couplingsupporting

confidence: 64%

Section: The Nucleus and Nucleo-cytoskeletal Couplingmentioning

confidence: 99%

Nucleus-Cytoskeleton Crosstalk During Mitotic Entry

Dantas

Lima

Ferreira

2021

Front. Cell Dev. Biol.

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“…Another possibility is that the decreased affinity of ΔNLS neurofibromins to actin ( Figure 1 and Table 1 ) may interfere with interactions of actin and MTs, as also demonstrated by the aberrant pattern of cell migration ( Figure 3 , Supplementary Figure S3 , and Supplementary Videos S1–3 ). Indeed, actin and MT interactions at the nuclear envelope during G2 may have significant impact on centrosome positioning for cell division and spindle orientation [ 91 , 92 ]. Lastly, we may not exclude the possibility, which has yet to be addressed, that the RasGAP activities of NLS and ΔNLS isoforms vary and thus different transcriptional regulation on MT nucleation regulators is exerted via Ras-dependent pathways.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Isoforms of Neurofibromin Are Required for Proper Spindle Organization and Chromosome Segregation

Peta

Tsirimonaki

Samouil

et al. 2020

Cells

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Mitotic spindles are highly organized, microtubule (MT)-based, transient structures that serve the fundamental function of unerring chromosome segregation during cell division and thus of genomic stability during tissue morphogenesis and homeostasis. Hence, a multitude of MT-associated proteins (MAPs) regulates the dynamic assembly of MTs in preparation for mitosis. Some tumor suppressors, normally functioning to prevent tumor development, have now emerged as significant MAPs. Among those, neurofibromin, the product of the Neurofibromatosis-1 gene (NF1), a major Ras GTPase activating protein (RasGAP) in neural cells, controls also the critical function of chromosome congression in astrocytic cellular contexts. Cell type- and development-regulated splicings may lead to the inclusion or exclusion of NF1exon51, which bears a nuclear localization sequence (NLS) for nuclear import at G2; yet the functions of the produced NLS and ΔNLS neurofibromin isoforms have not been previously addressed. By using a lentiviral shRNA system, we have generated glioblastoma SF268 cell lines with conditional knockdown of NLS or ΔNLS transcripts. In dissecting the roles of NLS or ΔNLS neurofibromins, we found that NLS-neurofibromin knockdown led to increased density of cytosolic MTs but loss of MT intersections, anastral spindles featuring large hollows and abnormal chromosome positioning, and finally abnormal chromosome segregation and increased micronuclei frequency. Therefore, we propose that NLS neurofibromin isoforms exert prominent mitotic functions.

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“…Inhibition of Arp2/3-dependent branched actin nucleation reduces this spindle-associated pool of actin and results in disorganized chromosome congression and mitotic defects [75]. Similarly, centrosome separation and positioning around the cell centroid are orchestrated by transient perinuclear actin and the LINC complex [76]. Actin filaments nucleated by formin-2 can even be found in the spindle itself during mitosis, working with microtubules to ensure faithful chromosome segregation [77].…”

Section: Actin Around the Nucleus During Mitosis And Meiosismentioning

confidence: 99%

Actin on and around the Nucleus

Davidson

Cadot

2021

Trends in Cell Biology

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Actin plays roles in many important cellular processes, including cell motility, organelle movement, and cell signaling. The discovery of transmembrane actin-binding proteins at the outer nuclear membrane (ONM) raises the exciting possibility that actin can play a role in direct force transmission to the nucleus and the genome at its interior. Actin-dependent nucleus displacement was first described a decade ago. We are now gaining a more detailed understanding of its mechanisms, as well as new roles for actin during mitosis and meiosis, for gene expression, and in the cell's response to mechanical stimuli. Here we review these recent developments, the actin-binding proteins involved, the tissue specificity of these mechanisms, and methods developed to reconstitute and study this interaction in vitro. Preamble: The Nucleus and the Surrounding ActinThe nucleus was once considered a simple, static reservoir for the genetic material of the cell. We now know that it plays a wide range of roles, from controlling mechanical sensing to regulating gene expression. Similarly, actin structures around the nuclear envelope (NE) (see Glossary) were first described decades ago, but their role was initially unclear. The discovery of the transmembrane linker of nucleoskeleton to cytoskeleton (LINC) complexes in the early 21st century established that nuclear lamins and chromatin inside the nucleus mechanically connect to the cytoskeleton outside the nucleus [1]. The NE and the actin cytoskeleton (Boxes 1 and 2) are now generating renewed interest as active partners in gene expression. NE proteins are implicated in a wide variety of diseases and their connections to actin may thus play important roles in many physiological processes, likely in a tissue-dependent manner (Figure 1).Here, we discuss the recently described roles that NE-associated actin plays, including displacement of the nucleus within the cell, NE breakdown (NEBD), gene expression, and cellular responses to stress. An entire parallel field has also risen from the (long controversial) idea that actin can assemble and perform functions inside the nucleus, although we do not discuss nuclear actin in this review. Actin Functions around the NucleusActin for Positioning Nuclei: Anchoring and Moving Nuclei into Position Actin mediates nuclear movement to a particular functional position within the cell in many tissues and is responsible for maintaining this position. One striking example is the interkinetic movement of nuclei in pseudostratified epithelia, first described in 1935 [2], in which nuclei are displaced from the basal to the apical surface of the cell to undergo mitosis. The roles of actin and microtubules in mediating nuclear movement differ significantly depending on the tissue, most likely due to the geometry and the thickness of the epithelial layer, which determine the mechanical constraints and the distance the nucleus must move [3]. Microtubules are required for nuclear movement in the highly elongated cells of the rodent neocortex, whereas in the zebra...

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Prophase-Specific Perinuclear Actin Coordinates Centrosome Separation and Positioning to Ensure Accurate Chromosome Segregation

Cited by 28 publications

References 73 publications

Nucleus-Cytoskeleton Crosstalk During Mitotic Entry

Nucleus-Cytoskeleton Crosstalk During Mitotic Entry

Nuclear Isoforms of Neurofibromin Are Required for Proper Spindle Organization and Chromosome Segregation

Actin on and around the Nucleus

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