scholarly journals Mapping the dynamics of force transduction at cell–cell junctions of epithelial clusters

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Mei Rosa Ng ◽  
Achim Besser ◽  
Joan S Brugge ◽  
Gaudenz Danuser

Force transduction at cell-cell adhesions regulates tissue development, maintenance and adaptation. We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters. Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell-cell junctions. At the multi-cellular scale, cell-cell force exchange depended on the cell position within a cluster, and was adaptive to reconfigurations due to cell divisions or positional rearrangements. Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors. These data provide insights into mechanisms that could control mechanical stress homeostasis in dynamic epithelial tissues, and highlight our methods as a resource for the study of mechanotransduction in cell-cell adhesions.

2021 ◽  
Author(s):  
Abhishek Mukherjee ◽  
Elisabeth Nadjar-Boger ◽  
Michael P. Sheetz ◽  
Haguy Wolfenson

AbstractThe physical interactions of cells with their external environment are critical for their survival and function. These interactions are altered upon epithelial to mesenchymal transition (EMT) as cells switch from relying primarily on cell-cell adhesions to relying on cell-matrix adhesions. Mechanical signals are central to regulating these two types of interactions, but the crosstalk and the mechanobiological processes that mediate the transition between them are poorly understood. Here we show that α-catenin, a mechanosensitive protein that regulates cadherin-based cell-cell adhesions, directly interacts with integrin adhesions and regulates their growth as well as their transmission of mechanical forces into the matrix. In mesenchymal cells, α-catenin is recruited to the cell edge where it interacts with actin in regions devoid of α-actinin. As actin and α-catenin flow from the cell edge toward the center, α-catenin interacts with vinculin within integrin adhesions to mediate adhesion maturation, enhance force transmission, and drive the proper assembly of actin stress fibers. Importantly, in the absence of α-catenin–vinculin interactions, cell adhesion to the matrix is impaired, and the cells display aberrant responses to matrix rigidity which is manifested in rigidity-independent growth. These results provide a novel understanding of α-catenin as having a dual-role in mechanosensing by both cell-cell and cell-matrix adhesions.


Author(s):  
Hao Ding ◽  
Ping Zhou ◽  
Wenxuan Fu ◽  
Lurong Ding ◽  
Weiliang Guo ◽  
...  
Keyword(s):  

1998 ◽  
Vol 111 (3) ◽  
pp. 347-357 ◽  
Author(s):  
S. Levenberg ◽  
B.Z. Katz ◽  
K.M. Yamada ◽  
B. Geiger

In this study we demonstrate that local stimulation of cell surface cadherins or integrins induces a selective enhancement of adherens junction or focal contact assembly, respectively, throughout the cell. N-cadherin transfected CHO cells (CHO-Ncad) were incubated with different ligands including N-cadherin extracellular domain (NEC), anti-N-cadherin antibodies, fibronectin and concanavalin A (ConA), conjugated to synthetic beads. Electron microscopic examination indicated that both cadherin- and integrin-reactive beads bound tightly to the cell surface and were apparently endocytosed after several hours of incubation. The ConA-beads remained largely at the cell surface. Immunofluorescence labeling of the cells with antibodies to different adhesion-associated molecules indicated that both NEC- and anti-N-cadherin-conjugated beads induced a major increase in the level of junction-associated cadherin and beta-catenin labeling and a modest increase in junctional vinculin labeling, compared to untreated cells or cells bound to ConA-beads. FN-conjugated beads, on the other hand, significantly enhanced vinculin labeling at focal contacts and suppressed cadherin and beta-catenin staining in cell-cell junctions. The cadherin-reactive beads specifically stimulated tyrosine phosphorylation at cell-cell junctions, while the FN-beads increased the levels of focal contact-associated phosphotyrosine, as shown by immunofluorescence labeling of the cells for phosphotyrosine. Inhibition of this phosphorylation by genistein resulted in a complete suppression of the effects of both types of beads. These findings indicate that specific cadherin- and integrin-mediated surface interactions can trigger positively cooperative long-range signaling events which lead to the selective assembly of cell-cell or cell-matrix adhesions, and that these signals involve tyrosine phosphorylation.


2007 ◽  
Vol 120 (16) ◽  
pp. 2828-2837 ◽  
Author(s):  
C.-Y. Bai ◽  
M. Ohsugi ◽  
Y. Abe ◽  
T. Yamamoto

2012 ◽  
Vol 109 (25) ◽  
pp. 9881-9886 ◽  
Author(s):  
M. L. McCain ◽  
H. Lee ◽  
Y. Aratyn-Schaus ◽  
A. G. Kleber ◽  
K. K. Parker

Biochemistry ◽  
2014 ◽  
Vol 53 (49) ◽  
pp. 7706-7717 ◽  
Author(s):  
Kris A. DeMali ◽  
Xiaowen Sun ◽  
Gabrielle A. Bui

2010 ◽  
Vol 21 (4) ◽  
pp. 584-596 ◽  
Author(s):  
Kazuomi Noda ◽  
Jianghui Zhang ◽  
Shigetomo Fukuhara ◽  
Satoshi Kunimoto ◽  
Michihiro Yoshimura ◽  
...  

Vascular endothelial (VE)-cadherin is a cell–cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin–dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell–cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell–cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, α-catenin, and β-catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of α- and β-catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that α-catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through α- and β-catenins are important for the stabilization of VE-cadherin at the cell–cell contacts in cAMP-Epac-Rap1 signal-activated cells.


PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38464 ◽  
Author(s):  
Qiusha Guo ◽  
Bing Xia ◽  
Feng Zhang ◽  
Mekel M. Richardson ◽  
Minghao Li ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Amélie Vernale ◽  
Maria Mandela Prünster ◽  
Fabio Marchianò ◽  
Henry Debost ◽  
Nicolas Brouilly ◽  
...  

Abstract Background The ancestral presence of epithelia in Metazoa is no longer debated. Porifera seem to be one of the best candidates to be the sister group to all other Metazoa. This makes them a key taxon to explore cell-adhesion evolution on animals. For this reason, several transcriptomic, genomic, histological, physiological and biochemical studies focused on sponge epithelia. Nevertheless, the complete and precise protein composition of cell–cell junctions and mechanisms that regulate epithelial morphogenetic processes still remain at the center of attention. Results To get insights into the early evolution of epithelial morphogenesis, we focused on morphogenic characteristics of the homoscleromorph sponge Oscarella lobularis. Homoscleromorpha are a sponge class with a typical basement membrane and adhaerens-like junctions unknown in other sponge classes. We took advantage of the dynamic context provided by cell dissociation-reaggregation experiments to explore morphogenetic processes in epithelial cells in a non-bilaterian lineage by combining fluorescent and electron microscopy observations and RNA sequencing approaches at key time-points of the dissociation and reaggregation processes. Conclusions Our results show that part of the molecular toolkit involved in the loss and restoration of epithelial features such as cell–cell and cell–matrix adhesion is conserved between Homoscleromorpha and Bilateria, suggesting their common role in the last common ancestor of animals. In addition, sponge-specific genes are differently expressed during the dissociation and reaggregation processes, calling for future functional characterization of these genes.


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