scholarly journals Structural centrosome aberrations sensitize polarized epithelia to basal cell extrusion

Open Biology ◽  
2018 ◽  
Vol 8 (6) ◽  
pp. 180044 ◽  
Author(s):  
Olivier Ganier ◽  
Dominik Schnerch ◽  
Erich A. Nigg
Keyword(s):  
Basal Cell ◽  
Cell Damage ◽  
Apical Surface ◽  
Basal Surface ◽  
Epithelial Monolayers ◽  
Metastatic Cells ◽  
Oncogenic Mutations ◽  
Promote Cell Survival ◽  
Polarized Epithelia ◽  
Cell Extrusion

Centrosome aberrations disrupt tissue architecture and may confer invasive properties to cancer cells. Here we show that structural centrosome aberrations, induced by overexpression of either Ninein-like protein (NLP) or CEP131/AZI1, sensitize polarized mammalian epithelia to basal cell extrusion. While unperturbed epithelia typically dispose of damaged cells through apical dissemination into luminal cavities, certain oncogenic mutations cause a switch in directionality towards basal cell extrusion, raising the potential for metastatic cell dissemination. Here we report that NLP-induced centrosome aberrations trigger the preferential extrusion of damaged cells towards the basal surface of epithelial monolayers. This switch in directionality from apical to basal dissemination coincides with a profound reorganization of the microtubule cytoskeleton, which in turn prevents the contractile ring repositioning that is required to support extrusion towards the apical surface. While the basal extrusion of cells harbouring NLP-induced centrosome aberrations requires exogenously induced cell damage, structural centrosome aberrations induced by excess CEP131 trigger the spontaneous dissemination of dying cells towards the basal surface from MDCK cysts. Thus, similar to oncogenic mutations, structural centrosome aberrations can favour basal extrusion of damaged cells from polarized epithelia. Assuming that additional mutations may promote cell survival, this process could sensitize epithelia to disseminate potentially metastatic cells.

An approach to the understanding of the clinical-etiopathological aspect of COVID-19 (SARS-CoV-2)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 862-869
Author(s):  
Meena Kumari ◽  
Monika Agrawal ◽  
Rakesh Kumar Singh ◽  
Parameswarappa S Byadgi
Keyword(s):  
World Health ◽  
Apical Surface ◽  
Therapy Assessment ◽  
Differentiated Cells ◽  
The World ◽  
Polarized Epithelia ◽  
Well Differentiated ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Epidemiological Characteristics

Currently, the world is facing a health and socioeconomic crisis caused by the novel coronavirus disease COVID-19. On 11 March 2020, the World Health Organization (WHO) has declared this disease as a pandemic. The condition (COVID-19) is an infectious disorder triggered by a newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2. Most of the COVID-19 infected patients will experience mild to moderate respiratory symptoms and recover without any unique therapy. Assessment of the clinical and epidemiological characteristics of SARS-CoV-2 cases suggests the infected patients will not be contagious until the onset of severe symptoms and affects the other organs. Well-differentiated cells of apical airway epithelia communicating with ACE2 were promptly infected to SARS-CoV-2 virus. But the expression of ACE 2 in poorly differentiated epithelia facilitated SARS spike (S) protein-pseudo typed virus entry and it is replicated in polarized epithelia and especially exited via the apical surface. Limiting the transmission of COVID-19 infection & its prevention can be regarded as a hierarchy of controls. In this article, we briefly discuss the most recent advances in respect to aetiology, pathogenesis and clinical progression of the disease COVID-19.

Pathophysiological correlates of two unique renal tubule lesions in rats with intestinal resection

2006 ◽  
Vol 291 (5) ◽  
pp. F1061-F1069 ◽  
Author(s):  
Elaine Worcester ◽  
Andrew Evan ◽  
Sharon Bledsoe ◽  
Mark Lyon ◽  
Mark Chuang ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Small Bowel ◽  
Bowel Resection ◽  
Cell Damage ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Renal Tissue ◽  
Apical Surface ◽  
Crystal Deposition ◽  
Oxalate Excretion

Rats with small bowel resection fed a high-oxalate diet develop extensive deposition of calcium oxalate (CaOx) and calcium phosphate crystals in the kidney after 4 mo. To explore the earliest sites of renal crystal deposition, rats received either small bowel resection or transection and were then fed either standard chow or a high-oxalate diet; perfusion-fixed renal tissue from five rats in each group was examined by light microscopy at 2, 4, 8, and 12 wk. Rats fed the high-oxalate diet developed birefringent microcrystals at the brush border of proximal tubule cells, with or without cell damage; the lesion was most common in rats with both resection and a high-oxalate diet (10/19 with the lesion) and was significantly correlated with urine oxalate excretion ( P < 0.001). Rats with bowel resection fed normal chow had mild hyperoxaluria but high urine CaOx supersaturation; four of these rats developed birefringent crystal deposition with tubule plugging in inner medullary collecting ducts (IMCD). Two rats fed a high-oxalate diet also developed this lesion, which was correlated with CaOx supersaturation, but not oxalate excretion. Tissue was examined under oil immersion, and tiny birefringent crystals were noted on the apical surface of IMCD cells only in animals with IMCD crystal plugging. In one animal, IMCD crystals were both birefringent and nonbirefringent, suggesting a mix of CaOx and calcium phosphate. Overall, these animals demonstrate two distinct sites and mechanisms of renal crystal deposition and may help elucidate renal lesions seen in humans with enteric hyperoxaluria and stones.

Extracellular glutamate flux regulates intracellular glutaminase activity in LLC-PK1-F+ cells

1995 ◽  
Vol 268 (6) ◽  
pp. C1418-C1424 ◽  
Author(s):  
T. C. Welbourne ◽  
X. Mu
Keyword(s):  
Time Course ◽  
Glutamate Uptake ◽  
Fold Increase ◽  
Cellular Level ◽  
Glutamine Metabolism ◽  
Apical Surface ◽  
Extracellular Glutamate ◽  
Basal Surface ◽  
F Cells ◽  
Glutaminase Activity

The role of extracellular glutamate flux in regulating intracellular glutaminase activity was assessed in confluent monolayers of proximal tubule-like LLC-PK1-F+ cells grown on porous supports. Glutamate is a well-known inhibitor of phosphate-dependent glutaminase (PDG). We hypothesized that, by restricting the flux of glutamate from the extracellular media, cellular level would fall, effecting deinhibition of the cellular glutaminase activity. To test this, cellular glutamate uptake and extracellular production were inhibited for 18 h by the addition of D-aspartate (10 mM) or acivicin (0.7 mM) to both apical and basal media. Inhibiting glutamate flux depressed cellular glutamate content 43 and 41%, respectively. Intracellular relative glutaminase activity, monitored as the breakdown of 14C-radiolabeled glutamine to glutamate, measured over 60 s in the presence of D-aspartate or acivicin showed a 2- to 2.5-fold increase with the fall in cellular glutamate. Interestingly, enhanced glutamine uptake after PDG deinhibition was predominantly expressed on the basal surface. Indeed, measuring glutamine utilization after gamma-glutamyltranspeptidase inhibition over the entire 18-h time course revealed inhibition at the apical surface but relative enhancement of uptake at the basal surface. The increased intracellular glutaminase pathway was also reflected in increased alanine production measured over the 18-h time course, despite the reduction in overall glutamine utilization. These results point to a major role for extracellular glutamate fluxes in regulating cellular glutamine metabolism and suggest that the intracellular pathway may be suppressed under these conditions.

Polarized properties of thyroid cells: A study with cultured porcine cells

1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S220-S224 ◽  
Author(s):  
Jean Mauchamp ◽  
Odile Chabaud ◽  
Marianne Chambard ◽  
Corinne Gerard ◽  
Claude Penel ◽  
...  
Keyword(s):  
Cell Layer ◽  
Culture Conditions ◽  
Thyroid Cell ◽  
Apical Surface ◽  
Cell Plasma Membrane ◽  
Basal Surface ◽  
Thyroid Cells ◽  
Cell Plasma ◽  
Apical Compartment ◽  
Cell Layers

Abstract. In primary culture porcine cells form polarized cell layers. We have designed culture conditions in which we can have access to only one side of the cell layer, either the apical or the basal surface. In addition, using culture chambers with permeable bottom we can have access to either side of the cell layer which separates two compartments. Using these organized systems we have shown that the iodide concentrating mechanism and the TSH-reseptor adenyl cyclase complex are localized on the basolateral domain of the thyroid cell plasma membrane. We also demonstrated the existence on the apical surface of an amiloride sensitive sodium uptake. Finally we observed that about 10% of newly synthesized thyroglobulin appears to be secreted directly into the basal compartment, 90% being secreted in the apical compartment.

Identification and expression analysis of the human μ-protocadherin gene in fetal and adult kidneys

2002 ◽  
Vol 283 (3) ◽  
pp. F454-F463 ◽  
Author(s):  
Michael Goldberg ◽  
Michelle Wei ◽  
Benjamin Tycko ◽  
Inna Falikovich ◽  
Dorothy Warburton
Keyword(s):  
Local Alignment ◽  
Apical Surface ◽  
Adhesive Interaction ◽  
Developmentally Regulated ◽  
Extracellular Region ◽  
Adult Kidney ◽  
Cellular Aggregation ◽  
Search Tool ◽  
Polarized Epithelia

We recently cloned μ-protocadherin, a developmentally regulated cell adhesion molecule that contains an extracellular region with four cadherin-like ectodomains and a triply repeating mucin domain in its longer isoform. Expression of μ-protocadherin in L929 cells resulted in cellular aggregation, confirming its role in intercellular adhesion. We now identify the human μ-protocadherin ortholog and study its distribution in vivo and its targeting in polarized epithelia. Basic Local Alignment Search Tool searches and fluorescent in situ hybridization analysis on the basis of human-mouse synteny reveal that μ-protocadherin maps to 11p15.5, matching a previously identified gene called MUCDHL. At least three different splicing isoforms exist for MUCDHL that vary in expression in the fetal kidney. μ-Protocadherin is apically expressed along the brush border of the proximal convoluted tubule of the adult kidney. Transfection of truncated forms of μ-protocadherin into polarized Madin-Darby canine kidney cells reveals that the NH2terminus is essential for targeting to the apical surface. These results suggest that although human μ-protocadherin may mediate a homotypic adhesive interaction, it may have additional functions in terminally differentiated epithelia.

scholarly journals Air-Liquid-Interface Differentiated Human Nose Epithelium: A Robust Primary Tissue Culture Model of SARS-CoV-2 Infection

2022 ◽  
Vol 23 (2) ◽  
pp. 835
Author(s):  
Bang M. Tran ◽  
Samantha L. Grimley ◽  
Julie L. McAuley ◽  
Abderrahman Hachani ◽  
Linda Earnest ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Cell Damage ◽  
Communicable Disease ◽  
Unmet Need ◽  
Liquid Interface ◽  
Apical Surface ◽  
Basal Cells ◽  
Clinical Model ◽  
Key Features ◽  
Air Liquid Interface

The global urgency to uncover medical countermeasures to combat the COVID-19 pandemic caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has revealed an unmet need for robust tissue culture models that faithfully recapitulate key features of human tissues and disease. Infection of the nose is considered the dominant initial site for SARS-CoV-2 infection and models that replicate this entry portal offer the greatest potential for examining and demonstrating the effectiveness of countermeasures designed to prevent or manage this highly communicable disease. Here, we test an air–liquid-interface (ALI) differentiated human nasal epithelium (HNE) culture system as a model of authentic SARS-CoV-2 infection. Progenitor cells (basal cells) were isolated from nasal turbinate brushings, expanded under conditionally reprogrammed cell (CRC) culture conditions and differentiated at ALI. Differentiated cells were inoculated with different SARS-CoV-2 clinical isolates. Infectious virus release into apical washes was determined by TCID50, while infected cells were visualized by immunofluorescence and confocal microscopy. We demonstrate robust, reproducible SARS-CoV-2 infection of ALI-HNE established from different donors. Viral entry and release occurred from the apical surface, and infection was primarily observed in ciliated cells. In contrast to the ancestral clinical isolate, the Delta variant caused considerable cell damage. Successful establishment of ALI-HNE is donor dependent. ALI-HNE recapitulate key features of human SARS-CoV-2 infection of the nose and can serve as a pre-clinical model without the need for invasive collection of human respiratory tissue samples.

scholarly journals Muscle scars in Porcellia (Gastropoda; Pleurotomariacea) from the Carboniferous of England

1986 ◽  
Vol 35 ◽  
pp. 53-58 ◽  
Author(s):  
John S. Peel
Keyword(s):  
Systematic Position ◽  
Apical Surface ◽  
Internal Mould ◽  
Basal Surface ◽  
Morphological Convergence

1\vo shell retractor muscles are described on an internal mould of Porcellia woodwardi, a pleurotomaria­cean gastropod from the Carboniferous of England. The scars are located at the junction between the um­bilical wall, and the apical surface and the basal surface, respectively. Similar positioning of muscle scars in Bellerophon of the same age reflects morphological convergence of the planispiral, anisostrophic Por-cellia with the planispiral, but isostrophic Bellerophon. It is concluded that the shape of muscle scars, in detail, can not contribute to solving the question of the systematic position of Bellerophon.

scholarly journals Hippo signaling promotes Ets21c-dependent apical cell extrusion in the Drosophila wing disc

2020 ◽  
Author(s):  
Xianlong Ai ◽  
Dan Wang ◽  
Junzheng Zhang ◽  
Jie Shen
Keyword(s):  
Basal Cell ◽  
Molecular Mechanisms ◽  
Apical Cell ◽  
Wing Disc ◽  
Epithelial Tissue ◽  
Hippo Signaling ◽  
Developmental Defects ◽  
Jnk Signaling ◽  
Signaling Activation ◽  
Cell Extrusion

ABSTRACTCell extrusion is a crucial regulator of epithelial tissue development and homeostasis. Epithelial cells undergoing apoptosis, bearing pathological mutations, and possessing developmental defects are actively extruded toward elimination. However, the molecular mechanisms of Drosophila epithelial cell extrusion are not fully understood. Here, we report that activation of the conserved Hippo (Hpo) signaling pathway induces both apical and basal cell extrusion in the Drosophila wing disc epithelia. We show that canonical Yorki targets Diap1, and that dMyc and Cyclin E are not required for either apical or basal cell extrusion induced by activation of this pathway. Another target gene, bantam, is only involved in basal cell extrusion, suggesting novel Hpo-regulated apical cell extrusion mechanisms. Using RNA-Seq analysis, we found that JNK signaling is activated in the extruding cells. We provide genetic evidence that JNK signaling activation is both sufficient and necessary for Hpo-regulated cell extrusion. Furthermore, we demonstrate that the ETS-domain transcription factor Ets21c, an ortholog of proto-oncogenes FLI1 and ERG, acts downstream of JNK signaling to mediate apical cell extrusion. Our findings reveal a novel molecular link between Hpo signaling and cell extrusion.SUMMARY STATEMENTActivation of Hippo signaling induces cell extrusion in the Drosophila wing epithelia, in which bantam mediates basal cell extrusion and Ets21c mediates apical cell extrusion.

scholarly journals Pili Binding to Asialo-GM1 on Epithelial Cells Can Mediate Cytotoxicity or Bacterial Internalization byPseudomonas aeruginosa

1999 ◽  
Vol 67 (7) ◽  
pp. 3207-3214 ◽  
Author(s):  
James C. Comolli ◽  
Leslie L. Waite ◽  
Keith E. Mostov ◽  
Joanne N. Engel
Keyword(s):  
Epithelial Cells ◽  
Cell Injury ◽  
Mdck Cells ◽  
Type Iv Pili ◽  
Receptor Interaction ◽  
Apical Surface ◽  
Epithelial Monolayers ◽  
Type Iv ◽  
Mediate Cytotoxicity ◽  
Asialo Gm1

ABSTRACT The interaction of Pseudomonas aeruginosa type IV pili and the glycosphingolipid asialo-GM1 (aGM1) can mediate bacterial adherence to epithelial cells, but the steps subsequent to this adherence have not been elucidated. To investigate the result of the interaction of pili and aGM1, we used polarized epithelial monolayers of Madin-Darby canine kidney (MDCK) cells in culture, which contained little detectable aGM1 on their apical surface but were able to incorporate exogenous aGM1. Compared to an untreated monolayer,P. aeruginosa PA103 displayed an eightfold increase in association with and fivefold more cytotoxicity toward MDCK cells pretreated with aGM1. Cytotoxicity of either carrier-treated or aGM1-treated monolayers required the type III secreted protein ExoU. Asialo-GM1 pretreatment of MDCK monolayers likewise augmented bacterial internalization of an isogenic invasive strain approximately fourfold. These increases were not seen in monolayers treated with GM1, the sialyated form of the glycolipid, and were inhibited by treatment with an antibody to aGM1. Also, the aGM1-mediated adhesion, cytotoxicity, and internalization required intact type IV pili since nonpiliated PA103 mutants were unaffected by aGM1 pretreatment of MDCK cells. These results demonstrate that epithelial cell injury and bacterial internalization can proceed from the same adhesin-receptor interaction, and they indicate that P. aeruginosa exoproducts solely determine the steps subsequent to adhesion.

Differentiated lines of cells from rabbit renal medullary thick ascending limbs grown on amnion

1985 ◽  
Vol 249 (1) ◽  
pp. C97-C104 ◽  
Author(s):  
N. Green ◽  
A. Algren ◽  
J. Hoyer ◽  
T. Triche ◽  
M. Burg
Keyword(s):  
Electron Microscopy ◽  
Functional Differentiation ◽  
The Other ◽  
Epithelial Tissue ◽  
Apical Surface ◽  
Tissue Cultures ◽  
Epithelial Monolayers ◽  
Zonula Occludens ◽  
Nephron Segment ◽  
Transepithelial Voltage

Previously we grew differentiated primary epithelial tissue cultures from rabbit renal medullary thick ascending limbs but were unable to subculture them into lines. Now, following the use of amnion as a support during the initial passages, two cell lines have grown from single fragments of medullary thick ascending limbs. Cells have now been in culture past 12 passages over more than 2 yr. On confluence they formed morphologically differentiated epithelial monolayers with polarization of the cells visible on electron microscopy. They had apical zonula occludens and microvilli, lateral cellular interdigitations, and basal membranes flat against the support. “Domes” often were visible when the epithelia formed on dishes, indicative of salt and water transport. Other functional differentiation in some passages of one line or the other included presence of Tamm-Horsfall protein (demonstrated by immunofluorescence) or transepithelial voltage oriented apical surface positive. Both the Tamm-Horsfall protein and the voltage are normally expressed by intact medullary thick ascending limbs and are characteristic of this particular nephron segment.

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