scholarly journals Force transduction by cadherin adhesions in morphogenesis

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1044 ◽  
Author(s):  
Willem-Jan Pannekoek ◽  
Johan de Rooij ◽  
Martijn Gloerich
Keyword(s):  
Adherens Junctions ◽  
Cell Behavior ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Cellular Behaviors ◽  
Intracellular Response ◽  
Cell Adhesions ◽  
Cell Intercalation ◽  
Cell Cell

Mechanical forces drive the remodeling of tissues during morphogenesis. This relies on the transmission of forces between cells by cadherin-based adherens junctions, which couple the force-generating actomyosin cytoskeletons of neighboring cells. Moreover, components of cadherin adhesions adopt force-dependent conformations that induce changes in the composition of adherens junctions, enabling transduction of mechanical forces into an intracellular response. Cadherin mechanotransduction can mediate reinforcement of cell–cell adhesions to withstand forces but also induce biochemical signaling to regulate cell behavior or direct remodeling of cell–cell adhesions to enable cell rearrangements. By transmission and transduction of mechanical forces, cadherin adhesions coordinate cellular behaviors underlying morphogenetic processes of collective cell migration, cell division, and cell intercalation. Here, we review recent advances in our understanding of this central role of cadherin adhesions in force-dependent regulation of morphogenesis.

scholarly journals P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

2016 ◽  
Vol 212 (2) ◽  
pp. 199-217 ◽  
Author(s):  
Cédric Plutoni ◽  
Elsa Bazellieres ◽  
Maïlys Le Borgne-Rochet ◽  
Franck Comunale ◽  
Agusti Brugues ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cell Biology ◽  
Cell Polarization ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Tumor Aggressiveness ◽  
And Migration ◽  
Cell Cell

Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

scholarly journals Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates epithelial reshaping

2011 ◽  
Vol 194 (4) ◽  
pp. 643-656 ◽  
Author(s):  
Katsutoshi Taguchi ◽  
Takashi Ishiuchi ◽  
Masatoshi Takeichi
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Mechanical Forces ◽  
Cell Adhesions ◽  
Cell Cell

The zonula adherens (ZA), a type of adherens junction (AJ), plays a major role in epithelial cell–cell adhesions. It remains unknown how the ZA is remodeled during epithelial reorganization. Here we found that the ZA was converted to another type of AJ with punctate morphology (pAJ) at the margins of epithelial colonies. The F-actin–stabilizing protein EPLIN (epithelial protein lost in neoplasm), which functions to maintain the ZA via its association with αE-catenin, was lost in the pAJs. Consistently, a fusion of αE-catenin and EPLIN contributed to the formation of ZA but not pAJs. We show that junctional tension was important for retaining EPLIN at AJs, and another force derived from actin fibers laterally attached to the pAJs inhibited EPLIN–AJ association. Vinculin was required for general AJ formation, and it cooperated with EPLIN to maintain the ZA. These findings suggest that epithelial cells remodel their junctional architecture by responding to mechanical forces, and the αE-catenin–bound EPLIN acts as a mechanosensitive regulator for this process.

scholarly journals Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Luis A Aparicio ◽  
Raquel Castosa ◽  
Mar Haz-Conde ◽  
Marta Rodríguez ◽  
Moisés Blanco ◽  
...  
Keyword(s):  
Tumour Cells ◽  
Epithelial Tumour ◽  
Cell Adhesions ◽  
Cell Cell

scholarly journals Mechanics of cell integration in vivo

2021 ◽  
Author(s):  
Guilherme Bastos Ventura ◽  
Aboutaleb Amiri ◽  
Raghavan Thiagarajan ◽  
Mari Tolonen ◽  
Amin Doostmohammadi ◽  
...  
Keyword(s):  
Critical Role ◽  
Surrounding Tissue ◽  
Mechanical Forces ◽  
Cell Tissue ◽  
Pulling Forces ◽  
Epithelial Junctions ◽  
Cellular Behaviors ◽  
Epithelial Sheet ◽  
Cell Intercalation

During embryonic development, regeneration and homeostasis, cells have to physically integrate into their target tissues, where they ultimately execute their function. Despite a significant body of research on how mechanical forces instruct cellular behaviors within the plane of an epithelium, very little is known about the mechanical interplay at the interface between migrating cells and their surrounding tissue, which has its own dynamics, architecture and identity. Here, using quantitative in vivo imaging and molecular perturbations, together with a theoretical model, we reveal that multiciliated cell (MCC) precursors in the Xenopus embryo form dynamic filopodia that pull at the vertices of the overlying epithelial sheet to probe their stiffness and identify the preferred positions for their integration into the tissue. Moreover, we report a novel function for a structural component of vertices, the lipolysis-stimulated lipoprotein receptor (LSR), in filopodia dynamics and show its critical role in cell intercalation. Remarkably, we find that pulling forces equip the MCCs to remodel the epithelial junctions of the neighboring tissue, enabling them to generate a permissive environment for their integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration.

scholarly journals A Novel Role of Nectins in Inhibition of the E-Cadherin–induced Activation of Rac and Formation of Cell-Cell Adherens Junctions

2004 ◽  
Vol 15 (3) ◽  
pp. 1077-1088 ◽  
Author(s):  
Takashi Hoshino ◽  
Kazuya Shimizu ◽  
Tomoyuki Honda ◽  
Tomomi Kawakatsu ◽  
Taihei Fukuyama ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
G Protein ◽  
Adherens Junctions ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Inhibitory Effect ◽  
Small G Protein ◽  
E Cadherin ◽  
Cell Cell

Nectins are Ca2+-independent immunoglobulin (Ig)-like cell-cell adhesion molecules. The trans-interactions of nectins recruit cadherins to the nectin-based cell-cell adhesion, resulting in formation of cell-cell adherens junctions (AJs) in epithelial cells and fibroblasts. The trans-interaction of E-cadherin induces activation of Rac small G protein, whereas the trans-interactions of nectins induce activation of not only Rac but also Cdc42 small G protein. We showed by the fluorescent resonance energy transfer (FRET) imaging that the trans-interaction of E-cadherin induced dynamic activation and inactivation of Rac, which led to dynamic formation and retraction of lamellipodia. Moreover, we found here that the nectins, which did not trans-interact with other nectins (non–trans-interacting nectins), inhibited the E-cadherin–induced activation of Rac and reduced the velocity of the formation of the E-cadherin-based cell-cell AJs. The inhibitory effect of non–trans-interacting nectins was suppressed by the activation of Cdc42 induced by the trans-interactions of nectins. These results indicate a novel role of nectins in regulation of the E-cadherin–induced activation of Rac and formation of cell-cell AJs.

scholarly journals α2β1 integrins spatially restrict Cdc42 activity to stabilise adherens junctions

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jake D. Howden ◽  
Magdalene Michael ◽  
Willow Hight-Warburton ◽  
Maddy Parsons
Keyword(s):  
Adherens Junctions ◽  
External Environment ◽  
Transmembrane Receptors ◽  
Matrix Cell ◽  
Keratinocyte Cell ◽  
Cell Adhesions ◽  
Cytoskeletal Networks ◽  
Α2β1 Integrin ◽  
Integrin Family ◽  
Cell Cell

Abstract Background Keratinocytes form the main protective barrier in the skin to separate the underlying tissue from the external environment. In order to maintain this barrier, keratinocytes form robust junctions between neighbouring cells as well as with the underlying extracellular matrix. Cell–cell adhesions are mediated primarily through cadherin receptors, whereas the integrin family of transmembrane receptors is predominantly associated with assembly of matrix adhesions. Integrins have been shown to also localise to cell–cell adhesions, but their role at these sites remains unclear. Results Here we show that α2β1 integrins are enriched at mature keratinocyte cell–cell adhesions, where they play a crucial role in organising cytoskeletal networks to stabilize adherens junctions. Loss of α2β1 integrin has significant functional phenotypes associated with cell–cell adhesion destabilisation, including increased proliferation, reduced migration and impaired barrier function. Mechanistically, we show that α2β1 integrins suppress activity of Src and Shp2 at cell–cell adhesions leading to enhanced Cdc42–GDI interactions and stabilisation of junctions between neighbouring epithelial cells. Conclusion Our data reveals a new role for α2β1 integrins in controlling integrity of epithelial cell–cell adhesions.

scholarly journals Non-junctional role of Cadherin3 in cell migration and contact inhibition of locomotion via domain-dependent, opposing regulation of Rac1

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Takehiko Ichikawa ◽  
Carsten Stuckenholz ◽  
Lance A. Davidson
Keyword(s):  
Cell Migration ◽  
Contact Inhibition ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Rac1 Activity ◽  
Classical Cadherins ◽  
Migration Assays ◽  
Spatio Temporal ◽  
Cell Cell

Abstract Classical cadherins are well-known adhesion molecules responsible for physically connecting neighboring cells and signaling this cell–cell contact. Recent studies have suggested novel signaling roles for “non-junctional” cadherins (NJCads); however, the function of cadherin signaling independent of cell–cell contacts remains unknown. In this study, mesendodermal cells and tissues from gastrula stage Xenopus laevis embryos demonstrate that deletion of extracellular domains of Cadherin3 (Cdh3; formerly C-cadherin in Xenopus) disrupts contact inhibition of locomotion. In both bulk Rac1 activity assays and spatio-temporal FRET image analysis, the extracellular and cytoplasmic Cdh3 domains disrupt NJCad signaling and regulate Rac1 activity in opposing directions. Stabilization of the cytoskeleton counteracted this regulation in single cell migration assays. Our study provides novel insights into adhesion-independent signaling by Cadherin3 and its role in regulating single and collective cell migration.

scholarly journals Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

2019 ◽  
Author(s):  
Azita Gorji ◽  
Pearlyn Jia Ying Toh ◽  
Yi-Chin Toh ◽  
Yusuke Toyama ◽  
Pakorn Kanchanawong
Keyword(s):  
Cell Migration ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Inhibitory Effect ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Combined Strategy ◽  
Cell Migration And Proliferation ◽  
Arterial Endothelial Cells ◽  
Cell Cell

RationaleFailure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases.ObjectivePrevious strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations.Methods and resultWe characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates.We identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization.Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation.ConclusionThe synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation.

scholarly journals Polar pattern formation induced by contact following locomotion in a multicellular system

2019 ◽  
Author(s):  
Masayuki Hayakawa ◽  
Tetsuya Hiraiwa ◽  
Yuko Wada ◽  
Hidekazu Kuwayama ◽  
Tatsuo Shibata
Keyword(s):  
Cell Migration ◽  
Mutant Cell ◽  
Cell Interaction ◽  
Collective Cell Migration ◽  
Contact Site ◽  
Band Formation ◽  
Polar Order ◽  
Agent Based ◽  
Cell Cell

AbstractBiophysical mechanisms underlying collective cell migration of eukaryotic cells have been studied extensively in recent years. One paradigm that induces cells to correlate their motions is contact inhibition of locomotion, by which cells migrating away from the contact site. Here, we report that tail-following behavior at the contact site, termed contact following locomotion (CFL), can induce a non-trivial collective behavior in migrating cells. We show the emergence of a traveling band showing polar order in a mutant Dictyostelium cell that lacks chemotactic activity. The traveling band is dynamic in the sense that it continuously assembled at the front of the band and disassembled at the back. A mutant cell lacking cell adhesion molecule TgrB1 did not show both the traveling band formation and CFL. We thus conclude that CFL is the cell-cell interaction underlying the traveling band formation. We then develop an agent-based simulation with CFL, which shows the role of CFL in the formation of traveling band. We further show that the polar order phase consists of subpopulations that exhibit characteristic transversal motions with respect to the direction of band propagation. These findings describe a novel mechanism of collective cell migration involving cell–cell interactions capable of inducing traveling band with polar order.

Sign in / Sign up

Export Citation Format

Share Document