Faculty Opinions recommendation of An instructive role for C. elegans E-cadherin in translating cell contact cues into cortical polarity.

The development of polarized epithelial cells from unpolarized precursor cells follows induction of cell-cell contacts and requires resorting of proteins into different membrane domains. We show that in MDCK cells the distributions of two membrane proteins, Dg-1 and E-cadherin, become restricted to the basal-lateral membrane domain within 8 h of cell-cell contact. During this time, however, 60-80% of newly synthesized Dg-1 and E-cadherin is delivered directly to the forming apical membrane and then rapidly removed, while the remainder is delivered to the basal-lateral membrane and has a longer residence time. Direct delivery of greater than 95% of these proteins from the Golgi complex to the basal-lateral membrane occurs greater than 48 h later. In contrast, we show that two apical proteins are efficiently delivered and restricted to the apical cell surface within 2 h after cell-cell contact. These results provide insight into mechanisms involved in the development of epithelial cell surface polarity, and the establishment of protein sorting pathways in polarized cells.

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Changes in E-cadherin rigidity sensing regulate cell adhesion

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1618676114 ◽

2017 ◽

Vol 114 (29) ◽

pp. E5835-E5844 ◽

Cited By ~ 34

Author(s):

Caitlin Collins ◽

Aleksandra K. Denisin ◽

Beth L. Pruitt ◽

W. James Nelson

Keyword(s):

Cell Adhesion ◽

Signaling Molecules ◽

Membrane Dynamics ◽

Cell Contact ◽

Adhesion Assay ◽

Cell Periphery ◽

Actin Organization ◽

Rigidity Sensing ◽

E Cadherin ◽

Cell Cell

Mechanical cues are sensed and transduced by cell adhesion complexes to regulate diverse cell behaviors. Extracellular matrix (ECM) rigidity sensing by integrin adhesions has been well studied, but rigidity sensing by cadherins during cell adhesion is largely unexplored. Using mechanically tunable polyacrylamide (PA) gels functionalized with the extracellular domain of E-cadherin (Ecad-Fc), we showed that E-cadherin–dependent epithelial cell adhesion was sensitive to changes in PA gel elastic modulus that produced striking differences in cell morphology, actin organization, and membrane dynamics. Traction force microscopy (TFM) revealed that cells produced the greatest tractions at the cell periphery, where distinct types of actin-based membrane protrusions formed. Cells responded to substrate rigidity by reorganizing the distribution and size of high-traction-stress regions at the cell periphery. Differences in adhesion and protrusion dynamics were mediated by balancing the activities of specific signaling molecules. Cell adhesion to a 30-kPa Ecad-Fc PA gel required Cdc42- and formin-dependent filopodia formation, whereas adhesion to a 60-kPa Ecad-Fc PA gel induced Arp2/3-dependent lamellipodial protrusions. A quantitative 3D cell–cell adhesion assay and live cell imaging of cell–cell contact formation revealed that inhibition of Cdc42, formin, and Arp2/3 activities blocked the initiation, but not the maintenance of established cell–cell adhesions. These results indicate that the same signaling molecules activated by E-cadherin rigidity sensing on PA gels contribute to actin organization and membrane dynamics during cell–cell adhesion. We hypothesize that a transition in the stiffness of E-cadherin homotypic interactions regulates actin and membrane dynamics during initial stages of cell–cell adhesion.

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Cell-to-cell contact influences proliferative marker expression and apoptosis in MIN6 cells grown in islet-like structures

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00424.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. E502-E509 ◽

Cited By ~ 40

Author(s):

Melanie J. Luther ◽

Emma Davies ◽

Dany Muller ◽

Moira Harrison ◽

Adrian J. Bone ◽

...

Keyword(s):

Cellular Proliferation ◽

Kinase Inhibitors ◽

Three Dimensional ◽

Cell Aggregation ◽

Cell Interactions ◽

Cell Phenotype ◽

Cell Contact ◽

Min6 Cells ◽

Primary Mouse ◽

E Cadherin

Cell-to-cell interactions play an important role in the development and maintenance of the β-cell phenotype. Here, we have investigated whether E-cadherin plays a role in regulating the growth of insulin-secreting MIN6 cells configured as three-dimensional islet-like clusters (pseudoislets). Pseudoislets form by cell aggregation rather than by proliferation from individual cells and attain the size of primary mouse islets after ∼7 days of maintenance in culture. E-cadherin is known to mediate homotypic cell adhesion between β-cells and has also been implicated in a number of cellular processes, including proliferation, apoptosis, and differentiation. E-cadherin and its associated intracellular elements, α- and β-catenin, were upregulated in MIN6 pseudoislets. Pseudoislet formation was associated with an increased expression of cyclin-dependent kinase inhibitors and a concomitant downregulation of Ki67, suggesting an overall reduction in cellular proliferation. However, measurements of 5-bromo-2′-deoxyuridine incorporation revealed that there were no differences in the rate of MIN6 cell proliferation whether they were configured as monolayers or as pseudoislets, which is likely to be a result of their being a transformed cell line. Cells within pseudoislets were not necrotic, but apoptosis appeared to be upregulated in the islet-like structures. However, no differential expression of Fas and FasL was detected in monolayers and pseudoislets. These results suggest that cell-to-cell interactions within islet-like structures may initiate antiproliferative and proapoptotic signals.

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Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00038.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. F511-F520 ◽

Cited By ~ 30

Author(s):

Hiroko Togawa ◽

Koichi Nakanishi ◽

Hironobu Mukaiyama ◽

Taketsugu Hama ◽

Yuko Shima ◽

...

Keyword(s):

Kidney Disease ◽

Epithelial Cells ◽

Polycystic Kidney Disease ◽

Autosomal Recessive ◽

Epithelial To Mesenchymal Transition ◽

Cell Contact ◽

Polycystic Kidney ◽

Mesenchymal Transition ◽

Cyst Lining ◽

E Cadherin

In polycystic kidney disease (PKD), cyst lining cells show polarity abnormalities. Recent studies have demonstrated loss of cell contact in cyst cells, suggesting induction of epithelial-to-mesenchymal transition (EMT). Recently, EMT has been implicated in the pathogenesis of PKD. To explore further evidence of EMT in PKD, we examined age- and segment-specific expression of adhesion molecules and mesenchymal markers in PCK rats, an orthologous model of human autosomal-recessive PKD. Kidneys from 5 male PCK and 5 control rats each at 0 days, 1, 3, 10, and 14 wk, and 4 mo of age were serially sectioned and stained with segment-specific markers and antibodies against E-cadherin, Snail1, β-catenin, and N-cadherin. mRNAs for E-cadherin and Snail1 were quantified by real-time PCR. Vimentin, fibronectin, and α-smooth muscle actin (α-SMA) expressions were assessed as mesenchymal markers. E-cadherin expression pattern was correlated with the disease pathology in that tubule segments showing the highest expression in control had much severer cyst formation in PCK rats. In PCK rats, E-cadherin and β-catenin in cystic tubules was attenuated and localized to lateral areas of cell-cell contact, whereas nuclear expression of Snail1 increased in parallel with cyst enlargement. Some epithelial cells in large cysts derived from these segments, especially in adjacent fibrotic areas, showed positive immunoreactivity for vimentin and fibronectin. In conclusion, these findings suggest that epithelial cells in cysts acquire mesenchymal features in response to cyst enlargement and participate in progressive renal fibrosis. Our study clarified the nephron segment-specific cyst profile related to EMT in PCK rats. EMT may play a key role in polycystic kidney disease.

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RNAi-Mediated Knock-Down of Arylamine N-acetyltransferase-1 Expression Induces E-cadherin Up-Regulation and Cell-Cell Contact Growth Inhibition

PLoS ONE ◽

10.1371/journal.pone.0017031 ◽

2011 ◽

Vol 6 (2) ◽

pp. e17031 ◽

Cited By ~ 40

Author(s):

Jacky M. Tiang ◽

Neville J. Butcher ◽

Carleen Cullinane ◽

Patrick O. Humbert ◽

Rodney F. Minchin

Keyword(s):

Growth Inhibition ◽

Cell Contact ◽

Knock Down ◽

E Cadherin ◽

Cell Cell

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Establishment of signaling interactions with cellular resolution for every cell cycle of embryogenesis

10.1101/285007 ◽

2018 ◽

Author(s):

Long Chen ◽

Vincy Wing Sze Ho ◽

Ming-Kin Wong ◽

Xiaotai Huang ◽

Lu-yan Chan ◽

...

Keyword(s):

Cell Cycle ◽

Notch Signaling ◽

Cell Lineage ◽

Cellular Interaction ◽

Cell Contact ◽

Contact Map ◽

C Elegans ◽

Cellular Resolution ◽

Signaling Interactions ◽

Lineage Analysis

AbstractIntercellular signaling interaction plays a key role in breaking fate symmetry during animal development. Identification of the signaling interaction at cellular resolution is technically challenging, especially in a developing embryo. Here we develop a platform that allows automated inference and validation of signaling interaction for every cell cycle of C. elegans embryogenesis. This is achieved by generation of a systems-level cell contact map that consists of 1,114 highly confident intercellular contacts by modeling analysis and is validated through cell membrane labeling coupled with cell lineage analysis. We apply the map to identify cell pairs between which a Notch signaling interaction takes place. By generating expression patterns for two ligands and two receptors of Notch signaling pathway with cellular resolution using automated expression profiling technique, we are able to refine existing and identify novel Notch interactions during C. elegans embryogenesis. Targeted cell ablation followed by cell lineage analysis demonstrates the roles of signaling interactions over cell division in breaking fate symmetry. We finally develop a website that allows online access to the cell-cell contact map for mapping of other signaling interaction in the community. The platform can be adapted to establish cellular interaction from any other signaling pathways.

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E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton

Journal of Cell Science ◽

10.1242/jcs.111.8.1071 ◽

1998 ◽

Vol 111 (8) ◽

pp. 1071-1080 ◽

Cited By ~ 6

Author(s):

S.M. Reuver ◽

C.C. Garner

Keyword(s):

Cell Adhesion ◽

Model Systems ◽

Molecular Organization ◽

Cell Contact ◽

Adhesion Sites ◽

Associated Proteins ◽

Adhesion Complex ◽

Cortical Cytoskeleton ◽

E Cadherin ◽

Cell Cell

Members of the SAP family of synapse-associated proteins have recently emerged as central players in the molecular organization of synapses. In this study, we have examined the mechanism that localizes one member, SAP97, to sites of cell-cell contact. Utilizing epithelial CACO-2 cells and fibroblast L-cells as model systems, we demonstrate that SAP97 is associated with the submembranous cortical cytoskeleton at cell-cell adhesion sites. Furthermore, we show that its localization into this structure is triggered by E-cadherin. Although SAP97 can be found in an E-cadherin/catenin adhesion complex, this interaction seems to be mediated by the attachment of SAP97 to the cortical cytoskeleton. Our results are consistent with a model in which SAP97 is recruited to sites of cell-cell contact via an E-cadherin induced assembly of the cortical cytoskeleton.

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Establishment of gut fate in the E lineage of C. elegans: the roles of lineage-dependent mechanisms and cell interactions

Development ◽

10.1242/dev.118.4.1267 ◽

1993 ◽

Vol 118 (4) ◽

pp. 1267-1277 ◽

Cited By ~ 14

Author(s):

B. Goldstein

Keyword(s):

Cell Interactions ◽

The Other ◽

Cell Contact ◽

Cell Stage ◽

C Elegans ◽

Daughter Cells ◽

Intact Embryo ◽

A Cell ◽

Random Position ◽

Recombination Experiments

The gut of C. elegans derives from all the progeny of the E blastomere, a cell of the eight cell stage. Previous work has shown that gut specification requires an induction during the four cell stage (Goldstein, B. (1992) Nature 357, 255–257). Blastomere isolation and recombination experiments were done to determine which parts of the embryo can respond to gut induction. Normally only the posterior side of the EMS blastomere contacts the inducing cell, P2. When P2 was instead placed in a random position on an isolated EMS, gut consistently differentiated from the daughter of EMS contacting P2, indicating that any side of EMS can respond to gut induction. Additionally, moving P2 around to the opposite side of EMS in an otherwise intact embryo caused EMS's two daughter cells to switch lineage timings, and gut to differentiate from the descendents of what normally would be the MS blastomere. The other cells of the four cell stage, ABa, ABp, and P2, did not form gut when placed in contact with the inducer. To determine whether any other inductions are involved in gut specification, timed blastomere isolations were done at the two and eight cell stages. In the absence of cell contact at the two cell stage, segregation of gut fate proceeded normally at both the two and four cell stages. Gut fate also segregated properly in the absence of cell contact at the eight cell stage. A model is presented for the roles of lineage-dependent mechanisms and cell interactions in establishing gut fate in the E lineage.

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