scholarly journals Force-dependent binding of vinculin to α-catenin regulates cell–cell contact stability and collective cell behavior

2018 ◽  
Vol 29 (4) ◽  
pp. 380-388 ◽  
Author(s):  
Rima Seddiki ◽  
Gautham Hari Narayana Sankara Narayana ◽  
Pierre-Olivier Strale ◽  
Hayri Emrah Balcioglu ◽  
Grégoire Peyret ◽  
...  
Keyword(s):  
Mechanical Load ◽  
Intercellular Junctions ◽  
Magnetic Tweezers ◽  
Contact Dynamics ◽  
Fine Tuning ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Mechanical Coupling ◽  
Contact Stability ◽  
Cell Cell

The shaping of a multicellular body and repair of adult tissues require fine-­tuning of cell adhesion, cell mechanics, and intercellular transmission of mechanical load. Adherens junctions (AJs) are the major intercellular junctions by which cells sense and exert mechanical force on each other. However, how AJs adapt to mechanical stress and how this adaptation contributes to cell–cell cohesion and eventually to tissue-scale dynamics and mechanics remains largely unknown. Here, by analyzing the tension-dependent recruitment of vinculin, α-catenin, and F-actin as a function of stiffness, as well as the dynamics of GFP-tagged wild-type and mutated α-catenins, altered for their binding capability to vinculin, we demonstrate that the force-dependent binding of vinculin stabilizes α-catenin and is responsible for AJ adaptation to force. Challenging cadherin complexes mechanical coupling with magnetic tweezers, and cell–cell cohesion during collective cell movements, further highlight that tension-dependent adaptation of AJs regulates cell–cell contact dynamics and coordinated collective cell migration. Altogether, these data demonstrate that the force-dependent α-catenin/vinculin interaction, manipulated here by mutagenesis and mechanical control, is a core regulator of AJ mechanics and long-range cell–cell interactions.

scholarly journals Force-dependent binding of vinculin to α-catenin regulates cell-cell contacts stability and collective cell behavior

2017 ◽  
Author(s):  
Rima Seddiki ◽  
Gautham Hari Narayana Sankara Narayana ◽  
Pierre-Olivier Strale ◽  
Hayri Emrah Balcioglu ◽  
Grégoire Peyret ◽  
...  
Keyword(s):  
Cell Biology ◽  
Mechanical Load ◽  
Magnetic Tweezers ◽  
Contact Dynamics ◽  
Fine Tuning ◽  
Biomechanical Analysis ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Mechanical Coupling ◽  
Cell Cell

AbstractThe shaping of a multicellular body and repair of adult tissues require fine-tuning of cell adhesion, cell mechanics and intercellular transmission of mechanical load. Adherens junctions (AJs) are the major intercellular junctions by which cells sense and exert mechanical force on each other. However, how AJs adapt to mechanical stress and how this adaptation contributes to cell-cell cohesion and eventually to tissue-scale dynamics and mechanics remains largely unknown. Here, by analyzing the tension-dependent recruitment of vinculin, α-catenin and F-actin as a function of stiffness, as well as the dynamics of GFP-tagged wild-type and mutated α-catenins, altered for their binding capability to vinculin, we demonstrate that the force-dependent binding of vinculin stabilizes α-catenin and is responsible for AJ adaptation to force. Challenging cadherin complexes mechanical coupling with magnetic tweezers, and cell-cell cohesion during collective cell movements, further highlight that tension-dependent adaptation of AJs regulates cell-cell contact dynamics and coordinated collective cell migration. Altogether, these data demonstrate that the force-dependent α-catenin/vinculin interaction, manipulated here by mutagenesis and mechanical control, is a core regulator of AJ mechanics and long-range cell-cell interactions.Summary statementCombining cell biology and biomechanical analysis, we show here that the coupling between cadherin complexes and actin trough tension-dependent α-catenin/vinculin association is regulating AJ stability and dynamics as well as tissue-scale mechanics.

scholarly journals The formation of ordered nanoclusters controls cadherin anchoring to actin and cell–cell contact fluidity

2015 ◽  
Vol 210 (2) ◽  
pp. 333-346 ◽  
Author(s):  
Pierre-Olivier Strale ◽  
Laurence Duchesne ◽  
Grégoire Peyret ◽  
Lorraine Montel ◽  
Thao Nguyen ◽  
...  
Keyword(s):  
Adherens Junction ◽  
Intercellular Junctions ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Contact Stability ◽  
Junction Formation ◽  
Mediate Cell ◽  
The Stability ◽  
E Cadherin ◽  
Cell Cell

Oligomerization of cadherins could provide the stability to ensure tissue cohesion. Cadherins mediate cell–cell adhesion by forming trans-interactions. They form cis-interactions whose role could be essential to stabilize intercellular junctions by shifting cadherin clusters from a fluid to an ordered phase. However, no evidence has been provided so far for cadherin oligomerization in cellulo and for its impact on cell–cell contact stability. Visualizing single cadherins within cell membrane at a nanometric resolution, we show that E-cadherins arrange in ordered clusters, providing the first demonstration of the existence of oligomeric cadherins at cell–cell contacts. Studying the consequences of the disruption of the cis-interface, we show that it is not essential for adherens junction formation. Its disruption, however, increased the mobility of junctional E-cadherin. This destabilization strongly affected E-cadherin anchoring to actin and cell–cell rearrangement during collective cell migration, indicating that the formation of oligomeric clusters controls the anchoring of cadherin to actin and cell–cell contact fluidity.

scholarly journals Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis

2019 ◽  
Vol 116 (10) ◽  
pp. 4291-4296 ◽  
Author(s):  
Taihei Fujimori ◽  
Akihiko Nakajima ◽  
Nao Shimada ◽  
Satoshi Sawai
Keyword(s):  
Cell Migration ◽  
Cell Movement ◽  
Tissue Level ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Contact Activation ◽  
Membrane Recruitment ◽  
Cell Rearrangement ◽  
Cell Protrusion ◽  
Cell Cell

Despite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain largely undefined. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning; however, in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoebaDictyostelium discoideumwhere the organizing center or the “tip” self-organizes as a result of sorting of differentiating prestalk and prespore cells. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode ofDictyosteliumcell migration that is strictly directed by cell–cell contact. The cell–cell contact signal is mediated by E-set Ig-like domain-containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of the SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude toward the contact signal as well as to chemotax toward cAMP; however, when given both signals, prestalk cells orient toward the chemoattractant, whereas prespore cells choose the contact signal. These data suggest a model of cell sorting by competing juxtacrine and diffusive cues, each with potential to drive its own mode of collective cell migration.

scholarly journals HIV-Captured DCs Regulate T Cell Migration and Cell-Cell Contact Dynamics to Enhance Viral Spread

iScience ◽  
2020 ◽  
Vol 23 (8) ◽  
pp. 101427 ◽  
Author(s):  
Wan Hon Koh ◽  
Paul Lopez ◽  
Oluwaseun Ajibola ◽  
Roshan Parvarchian ◽  
Umar Mohammad ◽  
...  
Keyword(s):  
Cell Migration ◽  
T Cell ◽  
Contact Dynamics ◽  
Cell Contact ◽  
Viral Spread ◽  
T Cell Migration ◽  
Cell Cell

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 Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis

2018 ◽  
Author(s):  
Taihei Fujimori ◽  
Akihiko Nakajima ◽  
Nao Shimada ◽  
Satoshi Sawai
Keyword(s):  
Cell Migration ◽  
Individual Cell ◽  
Cell Movement ◽  
Tissue Level ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Contact Activation ◽  
Cell Rearrangement ◽  
Cell Protrusion ◽  
Cell Cell

AbstractDespite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain much to be elucidated. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning, however in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoeba Dictyostelium discoideum where the organizing center or the ‘tip’ self-organize as a result of sorting of differentiating prestalk and prespore cells. Due to its relatively simple and conditional multicellularity, the system provides a rare case where the process can be fully dissected into individual cell behavior. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode of Dictyostelium cell migration that is strictly directed by cell-cell contact. The cell-cell contact signal is mediated by E-set Ig-like domain containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude towards the contact signal as well as to chemotax towards cAMP, however when given both signals, prestalk cells orient towards the chemoattractant whereas prespore cells choose the contact signal. These data suggest a new model of cell sorting by competing juxtacrine and diffusive cues each with potential to drive its own mode of collective cell migration. The present findings not only resolve the long standing question of how cells sort in Dictyostelium but also cast light on the remarkable parallels in collective cell migration that evolved independently in metazoa and amoebozoa.

Claudin-6 localized in tight junctions of rat podocytes

2008 ◽  
Vol 294 (6) ◽  
pp. R1856-R1862 ◽  
Author(s):  
Linning Zhao ◽  
Eishin Yaoita ◽  
Masaaki Nameta ◽  
Ying Zhang ◽  
Lino Munoz Cuellar ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Early Stage ◽  
Transmembrane Protein ◽  
Rat Kidney ◽  
Intercellular Junctions ◽  
Cell Contact ◽  
Puromycin Aminonucleoside ◽  
Contact Sites ◽  
Stage Of Development ◽  
Cell Cell

Tight junctions rarely exist in podocytes of the normal renal glomerulus, whereas they are the main intercellular junctions of podocytes in nephrosis and in the early stage of development. Claudins have been identified as tight junction-specific integral membrane proteins. Those of podocytes, however, remain to be elucidated. In the present study, we investigated the expression and localization of claudin-6 in the rat kidney, especially in podocytes. Western blot analysis and RT-PCR revealed that the neonatal kidney expressed much higher levels of claudin-6 than the adult kidney. Immunofluorescence microscopy showed intense claudin-6 staining in most of the tubules and glomeruli in neonates. The staining in tubules declined distinctly in adults, whereas staining in glomeruli was well preserved during development. Claudin-6 in glomeruli was distributed along the glomerular capillary wall and colocalized with zonula occludens-1. The staining became conspicuous after kidney perfusion with protamine sulfate (PS) to increase tight junctions in podocytes. Immunoelectron microscopy showed that immunogold particles for claudin-6 were accumulated at close cell-cell contact sites of podocytes in PS-perfused kidneys, whereas a very limited number of immunogold particles were detected, mainly on the basal cell membrane and occasionally at the slit diaphragm and close cell-cell contact sites in normal control kidneys. In puromycin aminonucleoside nephrosis, immunogold particles were also found mainly at cell-contact sites of podocytes. These findings indicate that claudin-6 is a transmembrane protein of tight junctions in podocytes during development and under pathological conditions.

scholarly journals Non-junctional Cadherin3 regulates cell migration and contact inhibition of locomotion via domain-dependent opposing regulations of Rac1

2019 ◽  
Author(s):  
Takehiko Ichikawa ◽  
Carsten Stuckenholz ◽  
Lance A. Davidson
Keyword(s):  
Cell Migration ◽  
Contact Inhibition ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Rac1 Activity ◽  
Classical Cadherins ◽  
The Stability ◽  
Cell Cell

AbstractClassical cadherins are well-known primary adhesion molecules responsible for physically connecting neighboring cells and signaling the cell-cell contact. Recent studies have suggested novel signaling roles for “non-junctional” cadherins (Niessen and Gottardi, 2008; Padmanabhan et al., 2017); however, the function of cadherin signaling independent of cell-cell contacts remains unknown. In this study, we used mesendoderm cells and tissues from gastrula stage Xenopus laevis embryos to demonstrate that extracellular and cytoplasmic cadherin domains regulate Rac1 in opposing directions in the absence of cell-cell contacts. Furthermore, we found that non-junctional cadherins regulate contact inhibition of locomotion (CIL) during gastrulation through alterations in the stability of the cytoskeleton. Live FRET imaging of Rac1 activity illustrated how non-junction cadherin3 (formerly C-cadherin) spatio-temporally regulates CIL. Our study provides novel insights into adhesion-independent signaling by cadherin3 and its role in regulating single and collective cell migration in vivo.

scholarly journals Laminin 511 partners with laminin 332 to mediate directional migration of Madin–Darby canine kidney epithelial cells

2012 ◽  
Vol 23 (1) ◽  
pp. 121-136 ◽  
Author(s):  
Patricia G. Greciano ◽  
Jose V. Moyano ◽  
Mary M. Buschmann ◽  
Jun Tang ◽  
Yue Lu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Laminin Receptor ◽  
Cell Contact ◽  
Spatial Cues ◽  
Madin Darby Canine Kidney ◽  
Directional Migration ◽  
Contact Stability ◽  
Darby Canine Kidney ◽  
Canine Kidney ◽  
Cell Cell

Sustained directional migration of epithelial cells is essential for regeneration of injured epithelia. Front–rear polarity of migrating cells is determined by local activation of a signaling network involving Cdc42 and other factors in response to spatial cues from the environment, the nature of which are obscure. We examined the roles of laminin (LM)-511 and LM-332, two structurally different laminin isoforms, in the migration of Madin–Darby canine kidney cells by suppressing expression of their α subunits using RNA interference. We determined that knockdown of LM-511 inhibits directional migration and destabilizes cell–cell contacts, in part by disturbing the localization and activity of the polarization machinery. Suppression of integrin α3, a laminin receptor subunit, in cells synthesizing normal amounts of both laminins has a similar effect as knockdown of LM-511. Surprisingly, simultaneous suppression of both laminin α5 and laminin α3 restores directional migration and cell–cell contact stability, suggesting that cells recognize a haptotactic gradient formed by a combination of laminins.

Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion

1998 ◽  
Vol 111 (4) ◽  
pp. 495-509 ◽  
Author(s):  
C. Marcozzi ◽  
I.D. Burdett ◽  
R.S. Buxton ◽  
A.I. Magee
Keyword(s):  
Cell Adhesion ◽  
Intercellular Junctions ◽  
Cell Aggregation ◽  
Cell Contact ◽  
Desmosomal Cadherins ◽  
Contact Sites ◽  
L Cells ◽  
Classical Cadherins ◽  
Adhesion Activity ◽  
Cell Cell

Desmosomes are unique intercellular junctions in that they invariably contain two types of transmembrane cadherin molecule, desmocollins and desmogleins. In addition they possess a distinct cytoplasmic plaque structure containing a few major proteins including desmoplakins and the armadillo family member plakoglobin. Desmosomal cadherins are putative cell-cell adhesion molecules and we have tested their adhesive capacity using a transfection approach in mouse L cells. We find that L cells expressing either one or both of the desmosomal cadherins desmocollin 2a or desmoglein 1 display weak cell-cell adhesion activity that is Ca2+-dependent. Both homophilic and heterophilic adhesion could be detected. However, co-expression of plakoglobin with both desmosomal cadherins, but not with desmoglein 1 alone, resulted in a dramatic potentiation of cell-cell aggregation and the accumulation of detergent-insoluble desmosomal proteins at points of cell-cell contact. The effect of plakoglobin seems to be due directly to its interaction with the desmosomal cadherins rather than to its signalling function. The data suggest that the desmosome may obligatorily contain two cadherins and is consistent with a model in which desmocollins and desmogleins may form side by side heterodimers in contrast to the classical cadherins that are homodimeric. Plakoglobin may function by potentiating dimer formation, accretion of dimers to cell-cell contact sites or desmosomal cadherin stability.

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