Molecular mechanisms regulating dissociation of cell-cell junction of epithelial cells by oxidative stress

2009 ◽  
Vol 14 (6) ◽  
pp. 703-716 ◽  
Author(s):  
Junko Inumaru ◽  
Osamu Nagano ◽  
Eri Takahashi ◽  
Takatsugu Ishimoto ◽  
Satoshi Nakamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Cell Junction ◽  
Cell Cell

scholarly journals Regulation of myosin activation during cell–cell contact formation by Par3-Lgl antagonism: entosis without matrix detachment

2012 ◽  
Vol 23 (11) ◽  
pp. 2076-2091 ◽  
Author(s):  
Qingwen Wan ◽  
Jing Liu ◽  
Zhen Zheng ◽  
Huabin Zhu ◽  
Xiaogang Chu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Myosin Ii ◽  
Coiled Coil ◽  
Host Cells ◽  
Cell Contact ◽  
Contact Formation ◽  
Cell Internalization ◽  
Mammary Gland Epithelial Cells ◽  
Cell Cell

Cell–cell contact formation following cadherin engagement requires actomyosin contraction along the periphery of cell–cell contact. The molecular mechanisms that regulate myosin activation during this process are not clear. In this paper, we show that two polarity proteins, partitioning defective 3 homologue (Par3) and mammalian homologues of Drosophila Lethal (2) Giant Larvae (Lgl1/2), antagonize each other in modulating myosin II activation during cell–cell contact formation in Madin-Darby canine kidney cells. While overexpression of Lgl1/2 or depletion of endogenous Par3 leads to enhanced myosin II activation, knockdown of Lgl1/2 does the opposite. Intriguingly, altering the counteraction between Par3 and Lgl1/2 induces cell–cell internalization during early cell–cell contact formation, which involves active invasion of the lateral cell–cell contact underneath the apical-junctional complexes and requires activation of the Rho–Rho-associated, coiled-coil containing protein kinase (ROCK)–myosin pathway. This is followed by predominantly nonapoptotic cell-in-cell death of the internalized cells and frequent aneuploidy of the host cells. Such effects are reminiscent of entosis, a recently described process observed when mammary gland epithelial cells were cultured in suspension. We propose that entosis could occur without matrix detachment and that overactivation of myosin or unbalanced myosin activation between contacting cells may be the driving force for entosis in epithelial cells.

scholarly journals Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ting Li ◽  
Yanhong Huang ◽  
Wenkai Zhou ◽  
Qichang Yan
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Western Blot ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Age Related ◽  
Spot Number ◽  
Gene Assay

Background. Oxidative stress is an important factor during age-related cataract formation. Apoptosis and autophagy induced by oxidative stress have been reported as key factors in age-related cataract. In our research, we investigated the role of let-7c-3p in the regulation of autophagy and apoptosis during the formation of age-related cataract. Material and Methods. Real-time PCR and western blot were employed to detect the expression of let-7c-3p in the tissues of age-related cataract. Human lens epithelial cells (LECs) were treated with H2O2 as an age-related cataract model. The extent of apoptosis was measured by flow cytometry and western blot. To detect autophagy, immunofluorescence was used to analyze the spot number of LC3, and western blot was used to detect the expression of LC3-II/I and ATG3. The molecular mechanisms of let-7c-3p regulating autophagy via ATG3 under oxidative stress were performed by a luciferase report gene assay and rescue experiment. Results. Downregulation of let-7c-3p was found in the age-related cataract group aged >65 years relative to the age-related cataract group aged ≤65 years. Consistently, the expression of let-7c-3p was also lower under oxidative stress. The activities of LEC apoptosis and autophagy induced by oxidative stress were inhibited by let-7c-3p. By the bioinformatics database and the luciferase reporter assay, ATG3 was found to be a direct target of let-7c-3p. Let-7c-3p reduced the ATG3-mediated autophagy level, which was induced by oxidative stress in LECs. Conclusion. Let-7c-3p inhibits autophagy by targeting ATG3 in LECs in age-related cataract.

Phosphatidylinositol-4-phosphate 5-kinase γ is associated with cell–cell junction in A431 epithelial cells

2005 ◽  
Vol 29 (7) ◽  
pp. 514-520 ◽  
Author(s):  
C AKIYAMA ◽  
N SHINOZAKINARIKAWA ◽  
T KITAZAWA ◽  
T HAMAKUBO ◽  
T KODAMA ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Junction ◽  
Phosphatidylinositol 4 ◽  
Cell Cell

scholarly journals Comprehensive analysis of formin localization in Xenopus epithelial cells

2019 ◽  
Vol 30 (1) ◽  
pp. 82-95 ◽  
Author(s):  
Tomohito Higashi ◽  
Rachel E. Stephenson ◽  
Ann L. Miller
Keyword(s):  
Epithelial Cells ◽  
Comprehensive Analysis ◽  
Cell Junctions ◽  
Actin Dynamics ◽  
Cell Junction ◽  
Contractile Ring ◽  
Dimerization Domain ◽  
Cellular Processes ◽  
And Function ◽  
Cell Cell

Reorganization of the actin cytoskeleton is crucial for cellular processes, including cytokinesis and cell–cell junction remodeling. Formins are conserved processive actin-polymerizing machines that regulate actin dynamics by nucleating, elongating, and bundling linear actin filaments. Because the formin family is large, with at least 15 members in vertebrates, there have not been any comprehensive studies examining formin localization and function within a common cell type. Here, we characterized the localization of all 15 formins in epithelial cells of Xenopus laevis gastrula-stage embryos. Dia1 and Dia2 localized to tight junctions, while Fhod1 and Fhod3 localized to adherens junctions. Only Dia3 strongly localized at the cytokinetic contractile ring. The Diaphanous inhibitory domain–dimerization domain (DID-DD) region of Dia1 was sufficient for Dia1 localization, and overexpression of a Dia1 DID-DD fragment competitively removed Dia1 and Dia2 from cell–cell junctions. In Dia1 DID-DD–overexpressing cells, Dia1 and Dia2 were mislocalized to the contractile ring, and cells exhibited increased cytokinesis failure. This work provides a comprehensive analysis of the localization of all 15 vertebrate formins in epithelial cells and suggests that misregulated formin localization results in epithelial cytokinesis failure.

scholarly journals EphA2 cleavage by MT1-MMP triggers single cancer cell invasion via homotypic cell repulsion

2013 ◽  
Vol 201 (3) ◽  
pp. 467-484 ◽  
Author(s):  
Nami Sugiyama ◽  
Erika Gucciardo ◽  
Olga Tatti ◽  
Markku Varjosalo ◽  
Marko Hyytiäinen ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Cell Surface ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Cell Junction ◽  
Physical Interaction ◽  
Surface Complexes ◽  
Human Breast Carcinomas ◽  
Cell Cell

Changes in EphA2 signaling can affect cancer cell–cell communication and motility through effects on actomyosin contractility. However, the underlying cell–surface interactions and molecular mechanisms of how EphA2 mediates these effects have remained unclear. We demonstrate here that EphA2 and membrane-anchored membrane type-1 matrix metalloproteinase (MT1-MMP) were selectively up-regulated and coexpressed in invasive breast carcinoma cells, where, upon physical interaction in same cell–surface complexes, MT1-MMP cleaved EphA2 at its Fibronectin type-III domain 1. This cleavage, coupled with EphA2-dependent Src activation, triggered intracellular EphA2 translocation, as well as an increase in RhoA activity and cell junction disassembly, which suggests an overall repulsive effect between cells. Consistent with this, cleavage-prone EphA2-D359I mutant shifted breast carcinoma cell invasion from collective to rounded single-cell invasion within collagen and in vivo. Up-regulated MT1-MMP also codistributed with intracellular EphA2 in invasive cells within human breast carcinomas. These results reveal a new proteolytic regulatory mechanism of cell–cell signaling in cancer invasion.

scholarly journals Diaphorina citri Nymphs Are Resistant to Morphological Changes Induced by “ Candidatus Liberibacter asiaticus” in Midgut Epithelial Cells

2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Marina Mann ◽  
Somayeh Fattah-Hosseini ◽  
El-Desouky Ammar ◽  
Richard Stange ◽  
EricaRose Warrick ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Morphological Changes ◽  
Diaphorina Citri ◽  
Content Type ◽  
Citrus Greening Disease ◽  
Mitochondrial Superoxide ◽  
Liberibacter Asiaticus

ABSTRACT “ Candidatus Liberibacter asiaticus” is the causative bacterium associated with citrus greening disease. “ Ca . Liberibacter asiaticus” is transmitted by Diaphorina citri more efficiently when it is acquired by nymphs rather than adults. Why this occurs is not known. We compared midguts of D. citri insects reared on healthy or “ Ca . Liberibacter asiaticus”-infected citrus trees using quantitative PCR, confocal microscopy, and mitochondrial superoxide staining for evidence of oxidative stress. Consistent with its classification as propagative, “ Ca . Liberibacter asiaticus” titers were higher in adults than in nymphs. Our previous work showed that adult D. citri insects have basal levels of karyorrhexis (fragmentation of the nucleus) in midgut epithelial cells, which is increased in severity and frequency in response to “ Ca . Liberibacter asiaticus.” Here, we show that nymphs exhibit lower levels of early-stage karyorrhexis than adults and are refractory to the induction of advanced karyorrhexis by “ Ca . Liberibacter asiaticus” in the midgut epithelium. MitoSox Red staining showed that guts of infected adults, particularly males, experienced oxidative stress in response to “ Ca . Liberibacter asiaticus.” A positive correlation between the titers of “ Ca . Liberibacter asiaticus” and the Wolbachia endosymbiont was observed in adult and nymph midguts, suggesting an interplay between these bacteria during development. We hypothesize that the resistance of the nymph midgut to late-stage karyorrhexis through as yet unknown molecular mechanisms benefits “ Ca . Liberibacter asiaticus” for efficient invasion of midgut epithelial cells, which may be a factor explaining the developmental dependency of “ Ca . Liberibacter asiaticus” acquisition by the vector.

scholarly journals The F-BAR domain of SRGP-1 facilitates cell–cell adhesion during C. elegans morphogenesis

2010 ◽  
Vol 191 (4) ◽  
pp. 761-769 ◽  
Author(s):  
Ronen Zaidel-Bar ◽  
Michael J. Joyce ◽  
Allison M. Lynch ◽  
Kristen Witte ◽  
Anjon Audhya ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Function Analysis ◽  
Membrane Dynamics ◽  
Protein Domain ◽  
Cell Junctions ◽  
Cell Junction ◽  
Loss Of Function ◽  
Bar Domain ◽  
Cell Cell

Robust cell–cell adhesion is critical for tissue integrity and morphogenesis, yet little is known about the molecular mechanisms controlling cell–cell junction architecture and strength. We discovered that SRGP-1 is a novel component of cell–cell junctions in Caenorhabditis elegans, localizing via its F-BAR (Bin1, Amphiphysin, and RVS167) domain and a flanking 200–amino acid sequence. SRGP-1 activity promotes an increase in membrane dynamics at nascent cell–cell contacts and the rapid formation of new junctions; in addition, srgp-1 loss of function is lethal in embryos with compromised cadherin–catenin complexes. Conversely, excess SRGP-1 activity leads to outward bending and projections of junctions. The C-terminal half of SRGP-1 interacts with the N-terminal F-BAR domain and negatively regulates its activity. Significantly, in vivo structure–function analysis establishes a role for the F-BAR domain in promoting rapid and robust cell adhesion during embryonic closure events, independent of the Rho guanosine triphosphatase–activating protein domain. These studies establish a new role for this conserved protein family in modulating cell–cell adhesion.

scholarly journals Accumulation of a microtubule-binding protein, pp170, at desmosomal plaques

1992 ◽  
Vol 117 (4) ◽  
pp. 813-824 ◽  
Author(s):  
IU Wacker ◽  
JE Rickard ◽  
JR De Mey ◽  
TE Kreis
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Mdck Cells ◽  
Binding Protein ◽  
Cell Junction ◽  
Microtubule Binding ◽  
Epithelial Cell Polarity ◽  
Junction Formation ◽  
Cell Cell

The establishment of epithelial cell polarity correlates with the formation of specialized cell-cell junctions and striking changes in the organization of microtubules. A significant fraction of the microtubules in MDCK cells become stabilized, noncentrosomally organized, and arranged in longitudinal bundles in the apical-basal axis. This correlation suggests a functional link between cell-cell junction formation and control of microtubule organization. We have followed the distribution of pp170, a recently described microtubule-binding protein, during establishment of epithelial cell polarity. This protein shows the typical patchy distribution along microtubules in subconfluent fibroblasts and epithelial cells, often associated with the peripheral ends of a subpopulation of microtubules. In contrast to its localization in confluent fibroblasts (A72) and HeLa cells, however, pp170 accumulates in patches delineating the regions of cell-cell contacts in confluent polarizing epithelial cells (MDCK and Caco-2). Double immunolocalization with antibodies specific for cell-cell junction proteins, confocal microscopy, and immunoelectron microscopy on polarized MDCK cells suggest that pp170 accumulates at desmosomal plaques. Furthermore, microtubules and desmosomes are found in close contact. Maintenance of the desmosomal association of pp170 is dependent on intact microtubules in 3-d-old, but not in 1-d-old MDCK cell cultures. This suggests a regulated interaction between microtubules and desmosomes and a role for pp170 in the control of changes in the properties of microtubules induced by epithelial cell-cell junction formation.

scholarly journals Endometrial profilin 1: a key player in embryo-endometrial crosstalk

2020 ◽  
Vol 47 (2) ◽  
pp. 114-121 ◽  
Author(s):  
Chang-Jin Lee ◽  
Seon-Hwa Hong ◽  
Min-Ji Yoon ◽  
Kyung-Ah Lee ◽  
Jung-Jae Ko ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Mouse Embryos ◽  
Implantation Failure ◽  
Cytoskeletal Networks ◽  
Endometrial Epithelial Cells ◽  
Embryo Attachment ◽  
Cell Cell

Objective: Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation.Methods: Morphological alterations depending on the status of PFN1 expression were assessed in PFN1-depleted or control cells grown on Matrigel-coated cover glass. Day-5 mouse embryos were cocultured with Ishikawa cells. Comparisons of the rates of F-actin formation and embryo attachment were performed by measuring the stability of the attached embryo onto PFN1-depleted or control cells.Results: Depletion of PFN1 in endometrial epithelial cells induced a significant reduction in cell-cell adhesion displaying less formation of colonies and a more circular cell shape. Mouse embryos co-cultured with PFN1-depleted cells failed to form actin cytoskeletal networks, whereas more F-actin formation in the direction of surrounding PFN1-intact endometrial epithelial cells was detected. Furthermore, significantly lower embryo attachment stability was observed in PFN1-depleted cells than in control cells. This may have been due to reduced endometrial receptivity caused by impaired actin cytoskeletal networks associated with PFN1 deficiency.Conclusion: These observations definitively demonstrate an important role of PFN1 in mediating cell-cell adhesion during the initial stage of embryo implantation and suggest a potential therapeutic target or novel biomarker for patients suffering from implantation failure.

scholarly journals Lulu2 regulates the circumferential actomyosin tensile system in epithelial cells through p114RhoGEF

2011 ◽  
Vol 195 (2) ◽  
pp. 245-261 ◽  
Author(s):  
Hiroyuki Nakajima ◽  
Takuji Tanoue
Keyword(s):  
Epithelial Cells ◽  
Cell Shape ◽  
Molecular Mechanisms ◽  
Molecular System ◽  
Apical Cell ◽  
Cell Junctions ◽  
Cellular Processes ◽  
Kinase C ◽  
Important Regulator ◽  
Cell Cell

Myosin II–driven mechanical forces control epithelial cell shape and morphogenesis. In particular, the circumferential actomyosin belt, which is located along apical cell–cell junctions, regulates many cellular processes. Despite its importance, the molecular mechanisms regulating the belt are not fully understood. In this paper, we characterize Lulu2, a FERM (4.1 protein, ezrin, radixin, moesin) domain–containing molecule homologous to Drosophila melanogaster Yurt, as an important regulator. In epithelial cells, Lulu2 is localized along apical cell–cell boundaries, and Lulu2 depletion by ribonucleic acid interference results in disorganization of the circumferential actomyosin belt. In its regulation of the belt, Lulu2 interacts with and activates p114RhoGEF, a Rho-specific guanine nucleotide exchanging factor (GEF), at apical cell–cell junctions. This interaction is negatively regulated via phosphorylation events in the FERM-adjacent domain of Lulu2 catalyzed by atypical protein kinase C. We further found that Patj, an apical cell polarity regulator, recruits p114RhoGEF to apical cell–cell boundaries via PDZ (PSD-95/Dlg/ZO-1) domain–mediated interaction. These findings therefore reveal a novel molecular system regulating the circumferential actomyosin belt in epithelial cells.

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