Faculty Opinions recommendation of Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance.

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.

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Analogous Telesensing Pathways Regulate Mating and Virulence in Two Opportunistic Human Pathogens

mBio ◽

10.1128/mbio.00181-10 ◽

2010 ◽

Vol 1 (4) ◽

Cited By ~ 3

Author(s):

Richard J. Bennett ◽

Gary M. Dunny

Keyword(s):

Sex Pheromones ◽

Genetic Material ◽

Fungal Species ◽

Genetic Exchange ◽

Cell Contact ◽

Human Pathogens ◽

Opportunistic Pathogens ◽

Pheromone Signaling ◽

Potential Partner ◽

Mediate Cell

ABSTRACT Telesensing, or probing of the environment by the release of chemical messengers, plays a central role in the sexual programs of microbial organisms. Sex pheromones secreted by mating cells are sensed by potential partner cells and mediate cell-to-cell contact and the subsequent exchange of genetic material. Although the mechanisms used by bacterial and fungal species to promote genetic exchange are distinct, recent studies have uncovered surprising parallels between pheromone signaling in these species. In addition, it is now apparent that pheromone signaling not only controls sexual reproduction and genetic exchange but can also activate expression of potential virulence factors in diverse opportunistic pathogens.

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A broadly distributed toxin family mediates contact-dependent antagonism between gram-positive bacteria

eLife ◽

10.7554/elife.26938 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 59

Author(s):

John C Whitney ◽

S Brook Peterson ◽

Jungyun Kim ◽

Manuel Pazos ◽

Adrian J Verster ◽

...

Keyword(s):

Critical Role ◽

Cell Contact ◽

Protein Fold ◽

Human Gut ◽

Gram Positive Bacteria ◽

Secretion Pathway ◽

Lipid Ii ◽

Mediate Cell ◽

Dependent Growth ◽

Dependent Mechanism

The Firmicutes are a phylum of bacteria that dominate numerous polymicrobial habitats of importance to human health and industry. Although these communities are often densely colonized, a broadly distributed contact-dependent mechanism of interbacterial antagonism utilized by Firmicutes has not been elucidated. Here we show that proteins belonging to the LXG polymorphic toxin family present in Streptococcus intermedius mediate cell contact- and Esx secretion pathway-dependent growth inhibition of diverse Firmicute species. The structure of one such toxin revealed a previously unobserved protein fold that we demonstrate directs the degradation of a uniquely bacterial molecule required for cell wall biosynthesis, lipid II. Consistent with our functional data linking LXG toxins to interbacterial interactions in S. intermedius, we show that LXG genes are prevalent in the human gut microbiome, a polymicrobial community dominated by Firmicutes. We speculate that interbacterial antagonism mediated by LXG toxins plays a critical role in shaping Firmicute-rich bacterial communities.

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Cell–cell contact landscapes in Xenopus gastrula tissues

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2107953118 ◽

2021 ◽

Vol 118 (39) ◽

pp. e2107953118

Author(s):

Debanjan Barua ◽

Martina Nagel ◽

Rudolf Winklbauer

Keyword(s):

Systematic Approach ◽

Cell Attachment ◽

Dominant Role ◽

Comprehensive Analysis ◽

Cell Contact ◽

Complex Interactions ◽

Contact Width ◽

Specific Contact ◽

Mediate Cell ◽

Cell Cell

Molecular and structural facets of cell–cell adhesion have been extensively studied in monolayered epithelia. Here, we perform a comprehensive analysis of cell–cell contacts in a series of multilayered tissues in the Xenopus gastrula model. We show that intercellular contact distances range from 10 to 1,000 nm. The contact width frequencies define tissue-specific contact spectra, and knockdown of adhesion factors modifies these spectra. This allows us to reconstruct the emergence of contact types from complex interactions of the factors. We find that the membrane proteoglycan Syndecan-4 plays a dominant role in all contacts, including narrow C-cadherin–mediated junctions. Glypican-4, hyaluronic acid, paraxial protocadherin, and fibronectin also control contact widths, and unexpectedly, C-cadherin functions in wide contacts. Using lanthanum staining, we identified three morphologically distinct forms of glycocalyx in contacts of the Xenopus gastrula, which are linked to the adhesion factors examined and mediate cell–cell attachment. Our study delineates a systematic approach to examine the varied contributions of adhesion factors individually or in combinations to nondiscrete and seemingly amorphous intercellular contacts.

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EphA2 Engages Git1 to Suppress Arf6 Activity Modulating Epithelial Cell–Cell Contacts

Molecular Biology of the Cell ◽

10.1091/mbc.e08-06-0549 ◽

2009 ◽

Vol 20 (7) ◽

pp. 1949-1959 ◽

Cited By ~ 52

Author(s):

Koichi Miura ◽

Jin-Min Nam ◽

Chie Kojima ◽

Naoki Mochizuki ◽

Hisataka Sabe

Keyword(s):

Ion Concentration ◽

Cell Contact ◽

Interacting Protein ◽

Cell Contacts ◽

Extracellular Signal ◽

Src Homology ◽

Src Homology 2 Domain ◽

Mediate Cell ◽

E Cadherin ◽

Cell Cell

ADP-ribosylation factor (Arf) 6 activity is crucially involved in the regulation of E-cadherin–based cell–cell adhesions. Erythropoietin-producing hepatocellular carcinoma (Eph)-family receptors recognize ligands, namely, ephrins, anchored to the membrane of apposing cells, and they mediate cell–cell contact-dependent events. Here, we found that Arf6 activity is down-regulated in Madin-Darby canine kidney cells, which is dependent on cell density and calcium ion concentration, and we provide evidence of a novel signaling pathway by which ligand-activated EphA2 suppresses Arf6 activity. This EphA2-mediated suppression of Arf6 activity was linked to the induction of cell compaction and polarization, but it was independent of the down-regulation of extracellular signal-regulated kinase 1/2 kinase activity. We show that G protein-coupled receptor kinase-interacting protein (Git) 1 and noncatalytic region of tyrosine kinase (Nck) 1 are involved in this pathway, in which ligand-activated EphA2, via its phosphorylated Tyr594, binds to the Src homology 2 domain of Nck1, and then via its Src homology 3 domain binds to the synaptic localizing domain of Git1 to suppress Arf6 activity. We propose a positive feedback loop in which E-cadherin–based cell–cell contacts enhance EphA-ephrinA signaling, which in turn down-regulates Arf6 activity to enhance E-cadherin–based cell–cell contacts as well as the apical-basal polarization of epithelial cells.

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Discovery and Characterization of Cadherin Domains in Saccharophagus degradans 2-40

Journal of Bacteriology ◽

10.1128/jb.01236-09 ◽

2009 ◽

Vol 192 (4) ◽

pp. 1066-1074 ◽

Cited By ~ 22

Author(s):

Milana Fraiberg ◽

Ilya Borovok ◽

Ronald M. Weiner ◽

Raphael Lamed

Keyword(s):

Protein Interactions ◽

Calcium Ions ◽

Calcium Ion ◽

Cell Contact ◽

Protein Protein Interactions ◽

Saccharophagus Degradans ◽

Mediate Cell ◽

Multiple Domains ◽

First Time

ABSTRACT Saccharophagus degradans strain 2-40 is a prominent member of newly discovered group of marine and estuarine bacteria that recycle complex polysaccharides. The S. degradans 2-40 genome codes for 15 extraordinary long polypeptides, ranging from 274 to 1,600 kDa. Five of these contain at least 52 cadherin (CA) and cadherin-like (CADG) domains, the types of which were reported to bind calcium ions and mediate protein/protein interactions in metazoan systems. In order to evaluate adhesive features of these domains, recombinant CA doublet domains (two neighboring domains) from CabC (Sde_3323) and recombinant CADG doublet domains from CabD (Sde_0798) were examined qualitatively and quantitatively for homophilic and heterophilic interactions. In addition, CA and CADG doublet domains were tested for adhesion to the surface of S. degradans 2-40. Results showed obvious homophilic and heterophilic, calcium ion-dependent interactions between CA and CADG doublet domains. Likewise, CA and CADG doublet domains adhered to the S. degradans 2-40 surface of cells that were grown on xylan from birch wood or pectin, respectively, as a sole carbon source. This research shows for the first time that bacterial cadherin homophilic and heterophilic interactions may be similar in their nature to cadherin domains from metazoan lineages. We hypothesize that S. degradans 2-40 cadherin and cadherin-like multiple domains contribute to protein-protein interactions that may mediate cell-cell contact in the marine environment.

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Cell-cell adhesion and signal transduction duringDictyosteliumdevelopment

Journal of Cell Science ◽

10.1242/jcs.114.24.4349 ◽

2001 ◽

Vol 114 (24) ◽

pp. 4349-4358 ◽

Cited By ~ 1

Author(s):

Juliet C. Coates ◽

Adrian J. Harwood

Keyword(s):

Signal Transduction ◽

Cell Adhesion ◽

Structural Integrity ◽

Adherens Junctions ◽

Cell Signalling ◽

Cell Junctions ◽

Cell Contact ◽

Multicellular Development ◽

Mediate Cell ◽

Cell Cell

The development of the non-metazoan eukaryote Dictyostelium discoideum displays many of the features of animal embryogenesis, including regulated cell-cell adhesion. During early development, two proteins, DdCAD-1 and csA, mediate cell-cell adhesion between amoebae as they form a loosely packed multicellular mass. The mechanism governing this process is similar to epithelial sheet sealing in animals. Although cell differentiation can occur in the absence of cell contact, regulated cell-cell adhesion is an important component of Dictyostelium morphogenesis, and a third adhesion molecule, gp150, is required for multicellular development past the aggregation stage.Cell-cell junctions that appear to be adherens junctions form during the late stages of Dictyostelium development. Although they are not essential to establish the basic multicellular body plan, these junctions are required to maintain the structural integrity of the fruiting body. The Dictyostelium β-catenin homologue Aardvark (Aar) is present in adherens junctions, which are lost in its absence. As in the case of its metazoan counterparts, Aar also has a function in cell signalling and regulates expression of the pre-spore gene psA.It is becoming clear that cell-cell adhesion is an integral part of Dictyostelium development. As in animals, cell adhesion molecules have a mechanical function and may also interact with the signal-transduction processes governing morphogenesis.

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Exosomes mediate cell contact–independent ephrin-Eph signaling during axon guidance

The Journal of Cell Biology ◽

10.1083/jcb.201601085 ◽

2016 ◽

Vol 214 (1) ◽

pp. 35-44 ◽

Cited By ~ 59

Author(s):

Jingyi Gong ◽

Roman Körner ◽

Louise Gaitanos ◽

Rüdiger Klein

Keyword(s):

Neural Development ◽

Tyrosine Kinases ◽

Neuronal Development ◽

Cell Types ◽

Cell Contact ◽

Eph Receptor ◽

Endosomal Sorting ◽

Ephrin Ligands ◽

Direct Cell ◽

Mediate Cell

The cellular release of membranous vesicles known as extracellular vesicles (EVs) or exosomes represents a novel mode of intercellular communication. Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands have very important roles in such biologically diverse processes as neuronal development, plasticity, and pathological diseases. Until now, it was thought that ephrin-Eph signaling requires direct cell contact. Although the biological functions of ephrin-Eph signaling are well understood, our mechanistic understanding remains modest. Here we report the release of EVs containing Ephs and ephrins by different cell types, a process requiring endosomal sorting complex required for transport (ESCRT) activity and regulated by neuronal activity. Treatment of cells with purified EphB2+ EVs induces ephrinB1 reverse signaling and causes neuronal axon repulsion. These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2+ EVs in neural development and synapse physiology.

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Cortical actin flow activates an alpha-catenin clutch to assemble adherens junctions

10.1101/2021.07.28.454239 ◽

2021 ◽

Author(s):

Ivar Noordstra ◽

Mario Diez Hermoso ◽

Lilian Schimmel ◽

Alexis Bonfim-Melo ◽

Joseph Mathew Kalappurakkal ◽

...

Keyword(s):

Adherens Junctions ◽

Actin Binding ◽

Cell Contact ◽

Cortical Actin ◽

Bond Behaviour ◽

Catch Bond ◽

Actin Cortex ◽

Mediate Cell ◽

E Cadherin ◽

Cell Cell

Adherens junctions (AJs) fundamentally mediate cell-cell adhesion, yet the mechanisms that determine where or when AJs assemble are not understood. Here we reveal a mechanosensitive clutch that initiates AJ assembly. Before cell-cell contact, alpha-catenin couples surface E-cadherin complexes to retrograde flow of the actin cortex. Cortical flows with opposed orientations persist after contact, applying tension to alpha-catenin within trans-ligated cadherin complexes. Tension unfolds the alpha-catenin actin-binding domain (ABD), which is expected to mediate a catch bond with F-actin. However, catch bond behaviour is not sufficient for AJ assembly in a molecular clutch model. Instead, it is also necessary for the activated ABD to promote cis-clustering of E-cadherin molecules by bundling F-actin. Thus, this alpha-catenin clutch transduces the mechanical signal of cortical flow to assemble AJs.

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