scholarly journals The nature of mitotic forces in epithelial monolayers

2020 ◽  
Author(s):  
Vivek K. Gupta ◽  
Sungmin Nam ◽  
Jaclyn Camuglia ◽  
Judy Lisette Martin ◽  
Erin Nicole Sanders ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Morphological Changes ◽  
Mitotic Cell ◽  
Force Generation ◽  
Model Organisms ◽  
Ring Contraction ◽  
Epithelial Monolayers ◽  
Dividing Cells ◽  
Chromosome Separation ◽  
Universal Mechanism

AbstractEpithelial cells undergo striking morphological changes during mitosis to ensure proper segregation of genetic and cytoplasmic materials. These morphological changes occur despite dividing cells being mechanically restricted by neighboring cells, indicating the need for extracellular force generation. While forces generated during mitotic rounding are well understood, forces generated after rounding remain unknown. Here, we identify two distinct stages of mitotic force generation that follow rounding: (1) protrusive forces along the mitotic axis that drive mitotic elongation, and (2) outward forces that facilitate post-mitotic re-spreading. Cytokinetic ring contraction of the mitotic cell, but not activity of neighboring cells, generates extracellular forces that propel mitotic elongation and also contribute to chromosome separation. Forces from mitotic elongation are observed in epithelia across many model organisms. Thus, forces from mitotic elongation represent a universal mechanism that powers mitosis in confining epithelia.

scholarly journals The nature of cell division forces in epithelial monolayers

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Vivek K. Gupta ◽  
Sungmin Nam ◽  
Donghyun Yim ◽  
Jaclyn Camuglia ◽  
Judy Lisette Martin ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Morphological Changes ◽  
Tissue Growth ◽  
Force Generation ◽  
Model Organisms ◽  
Epithelial Monolayers ◽  
Dividing Cells ◽  
Division Axis ◽  
Universal Mechanism

Epithelial cells undergo striking morphological changes during division to ensure proper segregation of genetic and cytoplasmic materials. These morphological changes occur despite dividing cells being mechanically restricted by neighboring cells, indicating the need for extracellular force generation. Beyond driving cell division itself, forces associated with division have been implicated in tissue-scale processes, including development, tissue growth, migration, and epidermal stratification. While forces generated by mitotic rounding are well understood, forces generated after rounding remain unknown. Here, we identify two distinct stages of division force generation that follow rounding: (1) Protrusive forces along the division axis that drive division elongation, and (2) outward forces that facilitate postdivision spreading. Cytokinetic ring contraction of the dividing cell, but not activity of neighboring cells, generates extracellular forces that propel division elongation and contribute to chromosome segregation. Forces from division elongation are observed in epithelia across many model organisms. Thus, division elongation forces represent a universal mechanism that powers cell division in confining epithelia.

scholarly journals An asymmetric junctional mechanoresponse coordinates mitotic rounding with epithelial integrity

2021 ◽  
Vol 220 (5) ◽  
Author(s):  
Jooske L. Monster ◽  
Lisa Donker ◽  
Marjolein J. Vliem ◽  
Zaw Win ◽  
Helen K. Matthews ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Morphological Changes ◽  
Mitotic Cell ◽  
Cell Junctions ◽  
Actin Binding ◽  
Epithelial Barrier ◽  
Epithelial Integrity ◽  
Tensile Forces ◽  
Shape Changes ◽  
Mitotic Cells

Epithelia are continuously self-renewed, but how epithelial integrity is maintained during the morphological changes that cells undergo in mitosis is not well understood. Here, we show that as epithelial cells round up when they enter mitosis, they exert tensile forces on neighboring cells. We find that mitotic cell–cell junctions withstand these tensile forces through the mechanosensitive recruitment of the actin-binding protein vinculin to cadherin-based adhesions. Surprisingly, vinculin that is recruited to mitotic junctions originates selectively from the neighbors of mitotic cells, resulting in an asymmetric composition of cadherin junctions. Inhibition of junctional vinculin recruitment in neighbors of mitotic cells results in junctional breakage and weakened epithelial barrier. Conversely, the absence of vinculin from the cadherin complex in mitotic cells is necessary to successfully undergo mitotic rounding. Our data thus identify an asymmetric mechanoresponse at cadherin adhesions during mitosis, which is essential to maintain epithelial integrity while at the same time enable the shape changes of mitotic cells.

scholarly journals Cbl-transforming Variants Trigger a Cascade of Molecular Alterations That Lead to Epithelial Mesenchymal Conversion

2000 ◽  
Vol 11 (10) ◽  
pp. 3397-3410 ◽  
Author(s):  
Tanya M. Fournier ◽  
Louie Lamorte ◽  
Christiane R. Maroun ◽  
Mark Lupher ◽  
Hamid Band ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Cell Spreading ◽  
Mesenchymal Transition ◽  
Amino Terminal ◽  
Src Homology ◽  
Hepatocyte Growth

Dispersal of epithelial cells is an important aspect of tumorigenesis, and invasion. Factors such as hepatocyte growth factor induce the breakdown of cell junctions and promote cell spreading and the dispersal of colonies of epithelial cells, providing a model system to investigate the biochemical signals that regulate these events. Multiple signaling proteins are phosphorylated in epithelial cells during hepatocyte growth factor–induced cell dispersal, including c-Cbl, a protooncogene docking protein with ubiquitin ligase activity. We have examined the role of c-Cbl and a transforming variant (70z-Cbl) in epithelial cell dispersal. We show that the expression of 70z-Cbl in Madin-Darby canine kidney epithelial cells resulted in the breakdown of cell–cell contacts and alterations in cell morphology characteristic of epithelial–mesenchymal transition. Structure–function studies revealed that the amino-terminal portion of c-Cbl, which corresponds to the Cbl phosphotyrosine-binding/Src homology domain 2 , is sufficient to promote the morphological changes in cell shape. Moreover, a point mutation at Gly-306 abrogates the ability of the Cbl Src homology domain 2 to induce these morphological changes. Our results identify a role for Cbl in the regulation of epithelial–mesenchymal transition, including loss of adherens junctions, cell spreading, and the initiation of cell dispersal.

Lactobacillus fermentum UCO-979C beneficially modulates the innate immune response triggered by Helicobacter pylori infection in vitro

2018 ◽  
Vol 9 (5) ◽  
pp. 829-841 ◽  
Author(s):  
V. Garcia-Castillo ◽  
H. Zelaya ◽  
A. Ilabaca ◽  
M. Espinoza-Monje ◽  
R. Komatsu ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Morphological Changes ◽  
Helicobacter Pylori Infection ◽  
Lactobacillus Fermentum ◽  
Gastric Tissue ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
H Pylori

Helicobacter pylori infection is associated with important gastric pathologies. An aggressive proinflammatory immune response is generated in the gastric tissue infected with H. pylori, resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. Probiotics could present an alternative solution to prevent or decrease H. pylori infection. Among them, the use of immunomodulatory lactic acid bacteria represents a promising option to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated its capacity to reduce adhesion of H. pylori to human gastric epithelial cells (AGS cells). In this work, the ability of L. fermentum UCO-979C to modulate immune response in AGS cells and PMA phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 (human monocytic leukaemia) macrophages in response to H. pylori infection was evaluated. We demonstrated that the UCO-979C strain is able to differentially modulate the cytokine response of gastric epithelial cells and macrophages after H. pylori infection. Of note, L. fermentum UCO-979C was able to significantly reduce the production of inflammatory cytokines and chemokines in AGS and THP-1 cells as well as increase the levels of immunoregulatory cytokines, indicating a remarkable anti-inflammatory effect. These findings strongly support the probiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Although our findings should be proven in appropriate experiments in vivo, in both H. pylori infection animal models and human trials, the results of the present work provide a scientific rationale for the use of L. fermentum UCO-979C to prevent or reduce H. pylori-induced gastric inflammation in humans.

scholarly journals A Septin Cytoskeleton-Targeting Small Molecule, Forchlorfenuron, Inhibits Epithelial Migration via Septin-Independent Perturbation of Cellular Signaling

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 84 ◽  
Author(s):  
Lei Sun ◽  
Xuelei Cao ◽  
Susana Lechuga ◽  
Alex Feygin ◽  
Nayden G. Naydenov ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cellular Systems ◽  
Model Organisms ◽  
Cellular Functions ◽  
Epithelial Migration ◽  
Cellular Processes ◽  
Dependent Inhibition ◽  
Erk Activity ◽  
Ht 29 ◽  
Target Effects

Septins are GTP-binding proteins that self-assemble into high-order cytoskeletal structures, filaments, and rings. The septin cytoskeleton has a number of cellular functions, including regulation of cytokinesis, cell migration, vesicle trafficking, and receptor signaling. A plant cytokinin, forchlorfenuron (FCF), interacts with septin subunits, resulting in the altered organization of the septin cytoskeleton. Although FCF has been extensively used to examine the roles of septins in various cellular processes, its specificity, and possible off-target effects in vertebrate systems, has not been investigated. In the present study, we demonstrate that FCF inhibits spontaneous, as well as hepatocyte growth factor-induced, migration of HT-29 and DU145 human epithelial cells. Additionally, FCF increases paracellular permeability of HT-29 cell monolayers. These inhibitory effects of FCF persist in epithelial cells where the septin cytoskeleton has been disassembled by either CRISPR/Cas9-mediated knockout or siRNA-mediated knockdown of septin 7, insinuating off-target effects of FCF. Biochemical analysis reveals that FCF-dependent inhibition of the motility of control and septin-depleted cells is accompanied by decreased expression of the c-Jun transcription factor and inhibited ERK activity. The described off-target effects of FCF strongly suggests that caution is warranted while using this compound to examine the biological functions of septins in cellular systems and model organisms.

scholarly journals Pre-akinete formation in Zygnema sp. from polar habitats is associated with metabolite re-arrangement

2020 ◽  
Vol 71 (11) ◽  
pp. 3314-3322 ◽  
Author(s):  
Erwann Arc ◽  
Martina Pichrtová ◽  
Ilse Kranner ◽  
Andreas Holzinger
Keyword(s):  
Environmental Conditions ◽  
Morphological Changes ◽  
Tca Cycle ◽  
Survival Strategies ◽  
Polar Regions ◽  
Akinete Formation ◽  
Metabolite Profiles ◽  
Dividing Cells ◽  
Storage Products ◽  
Chloroplast Morphology

Abstract In streptophytic green algae in the genus Zygnema, pre-akinete formation is considered a key survival strategy under extreme environmental conditions in alpine and polar regions. The transition from young, dividing cells to pre-akinetes is associated with morphological changes and the accumulation of storage products. Understanding the underlying metabolic changes could provide insights into survival strategies in polar habitats. Here, GC-MS-based metabolite profiling was used to study the metabolic signature associated with pre-akinete formation in Zygnema sp. from polar regions under laboratory conditions, induced by water and nutrient depletion, or collected in the field. Light microscopy and TEM revealed drastic changes in chloroplast morphology and ultrastructure, degradation of starch grains, and accumulation of lipid bodies in pre-akinetes. Accordingly, the metabolite profiles upon pre-akinete formation reflected a gradual shift in metabolic activity. Compared with young cells, pre-akinetes showed an overall reduction in primary metabolites such as amino acids and intermediates of the tricarboxylic acid (TCA) cycle, consistent with a lower metabolic turnover, while they accumulated lipids and oligosaccharides. Overall, the transition to the pre-akinete stage involves re-allocation of photosynthetically fixed energy into storage instead of growth, supporting survival of extreme environmental conditions.

Monochloramine induces reorganization of nuclear speckles and phosphorylation of SRp30 in human colonic epithelial cells: role of protein kinase C

2003 ◽  
Vol 285 (5) ◽  
pp. C1294-C1303 ◽  
Author(s):  
Ya-Qin Zhu ◽  
Yu Lu ◽  
Xiao-Di Tan
Keyword(s):  
Gastrointestinal Tract ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Morphological Changes ◽  
Sr Proteins ◽  
Mrna Splicing ◽  
Intestinal Epithelial ◽  
Nuclear Speckles ◽  
Colonic Epithelial Cells ◽  
Stimulation Of

Intestinal epithelial cells are constantly stimulated by reactive oxidant metabolites (ROMs) in inflamed mucosa. Monochloramine (NH2Cl), a cell-permeant ROM, is particularly relevant to the pathogenesis of inflammation in the gastrointestinal tract. Nuclear speckles, a unique nuclear subcompartment, accumulate a family of proteins, namely, serine- and arginine-rich (SR) proteins. They play important roles in regulation of pre-mRNA splicing. Currently, little is known about the link between inflammatory stimulation and the pre-mRNA splicing process, although gene expression is changed in inflamed tissues. The present study was designed to investigate whether stimulation of human colonic epithelial cells (HT-29 and Caco-2 cell lines) with NH2Cl affects nuclear speckles and their components. By indirect immunofluorescence, nuclear speckles have been shown to undergo rapid aggregation after NH2Cl stimulation. By utilizing Western blotting, SRp30 (a subset of SR proteins) in intestinal epithelial cells was found to be phosphorylated after NH2Cl treatment, whereas other SR proteins were not responsive to NH2Cl stimulation. The cytotoxic effect of NH2Cl was excluded by both negative lactate dehydrogenase assay and propidium iodide staining. Therefore, NH2Cl-induced morphological changes on nuclear speckles and phosphorylated SRp30 do not result from intestinal epithelial injury. Furthermore, the effect of NH2Cl on nuclear speckles and SRp30 was blocked by bisindolylmaleimide I, a selective PKC inhibitor. Together, the available data suggest that stimulation of intestinal epithelial cells with NH2Cl results in a consequent change on pre-mRNA splicing machinery via a distinctive signal pathway involving activation of PKC. This effect may contribute to oxidant-induced pathophysiological changes in the gastrointestinal tract.

Sign in / Sign up

Export Citation Format

Share Document