Contractile acto-myosin network on nuclear envelope remnants positions human chromosomes for mitosis

Booth, Alexander Jr; Yue, Zuojun; Eykelenboom, John K.; Stiff, Tom; Luxton, G. W. Gant; Hochegger, Helfrid; Tanaka, Tomoyuki

doi:10.7554/elife.46902

Cited by 38 publications

(49 citation statements)

References 30 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is important to note that there are changes in cell physiology just with time growing in culture. For example, Seaman et al have found that the nuclear morphology changes significantly over time in cultured human primary fibroblast cells [ 44 ]. Indeed, in our data both the GFP-KDEL and SUN1L-KDEL cells at 1G ( Table 1 ) show expected decrease in nuclear area and increase in nuclear height when comparing data from 2 h and 20 h in culture.…”

Section: Discussionmentioning

confidence: 99%

Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent

Neelam

Richardson

Barker

et al. 2020

IJMS

View full text Add to dashboard Cite

Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. In our study, we used a simulated microgravity device, a 3-D clinostat (Gravite), to investigate whether the LINC complex mediates cellular responses to the simulated microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth.

show abstract

Section: Discussionmentioning

confidence: 99%

Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent

Neelam

Richardson

Barker

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…We identified myosin IIA activity and the actin cytoskeleton as important for epidermal differentiation and Lamin A/C dispersal. Myosin II activity is required for nuclear repositioning in cell migration (Gomes, Jani, and Gundersen 2005), constriction of the cytokinetic actomyosin contractile ring (Powell 2005;De Lozanne and Spudich 1987;Mabuchi 1977) and contraction of an actin network around the nucleus at nuclear envelope breakdown (Booth et al 2019). Arp2/3, required for branched actin filament nucleation, has previously been identified as required for epidermal differentiation (Lechler 2014;Zhou et al 2013), regulation of nuclear actin (Oma and Harata 2011) and correct formation of the actomyosin contractile ring in cell division (Chan et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Akt1-associated actomyosin remodelling is required for nuclear lamina dispersal and nuclear shrinkage in epidermal terminal differentiation

Rogerson

Wotherspoon

O'Shaughnessy

2019

Preprint

View full text Add to dashboard Cite

Keratinocyte cornification and epidermal barrier formation are tightly controlled processes, which require complete degradation of intracellular organelles, including removal of keratinocyte nuclei. Keratinocyte nuclear destruction requires Akt1-dependent phosphorylation and degradation of the nuclear lamina protein, Lamin A/C, essential for nuclear integrity. However, the molecular mechanisms that result in complete nuclear removal and their regulation are not well defined. Post-confluent cultures of rat epidermal keratinocytes (REKs) undergo spontaneous and complete differentiation, allowing visualisation and perturbation of the differentiation process in vitro. We demonstrate that there is dispersal of phosphorylated Lamin A/C to structures throughout the cytoplasm in differentiating keratinocytes. We show that the dispersal of phosphorylated Lamin A/C is Akt1-dependent and these structures are specific for the removal of Lamin A/C from the nuclear lamina; nuclear contents and Lamin B were not present in these structures.Immunoprecipitation identified a group of functionally related Akt1 target proteins involved in Lamin A/C dispersal, including actin, which forms cytoskeletal microfilaments, Arp3, required for actin filament nucleation, and Myh9, a component of myosin IIa, a molecular motor that can translocate along actin filaments. Disruption of actin filament polymerisation, nucleation or myosin IIa activity prevented formation and dispersal of cytoplasmic Lamin A/C structures. Live imaging of keratinocytes expressing fluorescently tagged nuclear proteins showed a nuclear volume reduction step taking less than 40 minutes precedes final nuclear destruction. Preventing Akt1-dependent Lamin A/C phosphorylation and disrupting cytoskeletal Akt1associated proteins prevented nuclear volume reduction. Single cell RNA sequencing of differentiating keratinocytes identified gene changes correlated with lamin dispersal, which we propose are due to changes in lamina-associated domains upon Lamin A/C dispersal. We propose keratinocyte nuclear destruction and differentiation requires myosin II activity and the actin cytoskeleton for two intermediate processes: Lamin A/C dispersal and rapid nuclear volume reduction.

show abstract

“…, 2014 ; Plessner et al. , 2019 ), and its accumulation on the nuclear envelope (NE) facilitates chromosome congression ( Booth et al. , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Centrosome–nuclear axis repositioning drives the assembly of a bipolar spindle scaffold to ensure mitotic fidelity

Nunes

Dantas

Castro

et al. 2020

MBoC

View full text Add to dashboard Cite

show abstract

Contractile acto-myosin network on nuclear envelope remnants positions human chromosomes for mitosis

Cited by 38 publications

References 30 publications

Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent

Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent

Akt1-associated actomyosin remodelling is required for nuclear lamina dispersal and nuclear shrinkage in epidermal terminal differentiation

Centrosome–nuclear axis repositioning drives the assembly of a bipolar spindle scaffold to ensure mitotic fidelity

Contact Info

Product

Resources

About