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Article
| Open Access
Plakoglobin is a mechanoresponsive regulator of naive pluripotency
The mechanical microenvironment influences stem cell pluripotency. Here, the authors culture stem cells in microgels with controlled volumetric confinement and identify Plakoglobin as a mechanoresponsive regulator of pluripotency in mouse and human.
- Timo N. Kohler
- , Joachim De Jonghe
- & Florian Hollfelder
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| Open Access
TRIM40 is a pathogenic driver of inflammatory bowel disease subverting intestinal barrier integrity
The cortical actin cytoskeleton plays a role in maintaining intestinal epithelial integrity. Here the authors report that TRIM40, an E3 ligase, disrupts cortical actin formation and leads to loss of epithelial barrier integrity, and that genetic loss of TRIM40 is protective against experimental colitis in male mice.
- Sujin Kang
- , Jaekyung Kim
- & Boyoun Park
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| Open Access
Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation
The epithelial protein Coxsackievirus Adenovirus Receptor (CAR) is a virus receptor but may have other functions. Here the authors show that deletion of CAR in mice leads to reduced house dust mite-induced lung inflammation, reduced neutrophil accumulation and alterations in airway remodelling.
- Elena Ortiz-Zapater
- , Dustin C. Bagley
- & Maddy Parsons
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| Open Access
Afadin couples RAS GTPases to the polarity rheostat Scribble
Goudreault et al. investigate the role of Afadin downstream of RAS GTPases, substantiating this cell adhesion protein as a true RAS effector that couples its activation to cell polarity through the Scribble protein.
- Marilyn Goudreault
- , Valérie Gagné
- & Matthew J. Smith
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Article
| Open Access
Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability
Functional vascular tree formation is a key step in many contexts, such as cancer, and Neuropilin1 (NRP1) has been associated with adhesion receptor endocytic turnover. Here, authors show NRP1 and its mini-WARS ligand play a role in reducing endothelial permeability.
- Noemi Gioelli
- , Lisa J. Neilson
- & Guido Serini
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| Open Access
Topography-induced large-scale antiparallel collective migration in vascular endothelium
The physical environment dictates the emergence of specific patterns of collective cell migration. Here, authors show that unconfined endothelial monolayers on microgroove substrates exhibit an original pattern of antiparallel cell streams.
- Claire Leclech
- , David Gonzalez-Rodriguez
- & Abdul I. Barakat
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Article
| Open Access
α-catenin switches between a slip and an asymmetric catch bond with F-actin to cooperatively regulate cell junction fluidity
By using laser tweezers, the authors show that a single α-catenin molecule does not resist force on F-actin. However, clustering of multiple molecules and force applied toward F-actin pointed end engage a molecular switch in α-catenin, which unfolds and strongly binds F-actin.
- C. Arbore
- , M. Sergides
- & M. Capitanio
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| Open Access
Tissue fluidity mediated by adherens junction dynamics promotes planar cell polarity-driven ommatidial rotation
Ommatidial rotation in the Drosophila eye is a regulated process and a Planar Cell Polarity (PCP) cell motility model. Here, the authors show that tissue fluidity via junctional remodeling, as regulated by the PCP effector kinase Nemo, is critical for this cell motility process.
- Nabila Founounou
- , Reza Farhadifar
- & Marek Mlodzik
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Article
| Open Access
Physical basis for the determination of lumen shape in a simple epithelium
The formation of a hollow lumen surrounded by cells is a key developmental process that sets the shape of tissues and organs. Here, the authors show how the combined influence of geometric constraints imposed by cell packing and osmotic pressure can generate the diverse range in lumen shapes observed in different tissues.
- Claudia G. Vasquez
- , Vipul T. Vachharajani
- & Alexander R. Dunn
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| Open Access
Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of β-catenin signaling
Endothelial tissues must have intact barrier function, but this may be disrupted during inflammation. Here, the authors show that the mitochondrial protein Mitofusin-2 stabilizes cell–cell adherens junctions in endothelial cells during homeostasis and binds the transcriptional activator β-catenin upon inflammatory stimulation.
- Young-Mee Kim
- , Sarah Krantz
- & Jalees Rehman
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Article
| Open Access
A junctional PACSIN2/EHD4/MICAL-L1 complex coordinates VE-cadherin trafficking for endothelial migration and angiogenesis
Communication between endothelial leader and follower cells during collective cell migration is crucial for vascular development. Here, the authors show that PACSIN2 guides collective cell migration and angiogenesis by recruiting a protein trafficking complex to asymmetric cell-cell junctions, controlling local junction plasticity.
- Tsveta S. Malinova
- , Ana Angulo-Urarte
- & Stephan Huveneers
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Article
| Open Access
E-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow
The arrival of migratory cells at their targets relies on following precise routes within tissues. Here the authors demonstrate that the cell adhesion molecule E-cadherin can control the path of cell migration by confining the site where bleb-type protrusions form within the cell front.
- Cecilia Grimaldi
- , Isabel Schumacher
- & Erez Raz
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Article
| Open Access
β-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis
Multicellular rosettes are known to mediate complex cellular reorganization such as epithelial folding and branching during embryonal organogenesis. Here the authors show that rosette formation regulated by β-Catenin and FGFR2 mediate postnatal adrenal cortex zona glomerulosa morphogenesis.
- Sining Leng
- , Emanuele Pignatti
- & David T. Breault
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| Open Access
ZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer
Non-small cell lung cancer (NSCLC) is often associated with metastasis to the lungs. Here, the authors perform independent screens and identify NuRD as a co-repressor of ZEB1, and demonstrate TBC1D2b as a downstream target of ZEB1/NuRD complex regulating NSCLC metastasis.
- Roxsan Manshouri
- , Etienne Coyaud
- & Don L. Gibbons
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| Open Access
Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions
Cell-cell adhesion mediated by catenin-cadherin complexes plays a critical role in translating the mechanical forces into physiological responses. Here the authors define a mechanism of force-dependent cadherin-actin linkage dynamically regulated through the actin-binding domain of α-catenin.
- Noboru Ishiyama
- , Ritu Sarpal
- & Mitsuhiko Ikura
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| Open Access
Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin-F-actin based oscillatory cell-cell interaction
During the formation of the zebrafish dorsal longitudinal anastomotic vessel, blood vessels connect in a process called anastomosis. Using live imaging, the authors here show that endothelial cell movements during blood vessel anastomosis are associated with oscillating lamellipodia-like structures, oriented in the direction of the movements and emerging at endothelial cell junctions.
- Ilkka Paatero
- , Loïc Sauteur
- & Heinz-Georg Belting
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Article
| Open Access
SOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2α
Tumour vasculature influences drug delivery. Here, the authors show that SOD3 re-expression enhances doxorubicin delivery and effects through normalization of tumour vasculature via the HIF-2a/VE-cadherin pathway.
- Emilia Mira
- , Lorena Carmona-Rodríguez
- & Santos Mañes
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| Open Access
Polarized actin and VE-cadherin dynamics regulate junctional remodelling and cell migration during sprouting angiogenesis
The formation of new blood vessels requires both polarized cell migration and coordinated control of endothelial cell contacts. Here, Cao and colleagues describe at the sub-cellular level the cytoskeletal and cell junction dynamics regulating these processes upon VEGF-induced cell elongation.
- Jiahui Cao
- , Manuel Ehling
- & Hans Schnittler
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| Open Access
Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells
Cancer cells can disrupt cell-to-cell junctions, thus allowing migration and metastasis. Here starting from a chemical screening, Ito et al. reconstitute a step-by-step mechanism linking microtubule depolymerization and epithelial cell junction restoration.
- Shoko Ito
- , Satoru Okuda
- & Masatoshi Takeichi
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| Open Access
E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning
In multi-layered epithelia tight junctions (TJ) are confined to the most suprabasal viable layer. Here the authors show that this is regulated by ubiquitously localized E-cadherin tuning junctional tension and EGFR activity to inhibit TJ formation in lower layers while promoting TJ stability in the granular layer 2.
- Matthias Rübsam
- , Aaron F. Mertz
- & Carien M. Niessen
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| Open Access
Apical surface supracellular mechanical properties in polarized epithelium using noninvasive acoustic force spectroscopy
Determination of apical tension, fluidity, and intercellular adhesive forces in an epithelial monolayer are currently disruptive. Here the authors present a method using acoustic force microscopy to measure changes in these parameters upon tight junction structural alterations in a MDCK monolayer.
- Alexander X. Cartagena-Rivera
- , Christina M. Van Itallie
- & Richard S. Chadwick
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| Open Access
Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1
Epithelial cell-cell adhesions are contractile junctions, but whether contractility can be down-regulated is not known. Here the authors report how tyrosine dephosphorylation of the cytoskeletal scaffold, cortactin, recruits the RhoA antagonist SRGAP1 to relax adherens junctions in response to HGF.
- Xuan Liang
- , Srikanth Budnar
- & Alpha S. Yap
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| Open Access
Planar polarized Rab35 functions as an oscillatory ratchet during cell intercalation in the Drosophila epithelium
Various stages of tissue morphogenesis involve the contraction of epithelial surfaces. Here, the authors identify the Rab GTPase Rab35 as an essential component of this contractile process, which functions as a membrane ratchet to ensure unidirectional movement of intercalating cells.
- Cayla E. Jewett
- , Timothy E. Vanderleest
- & J. Todd Blankenship
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| Open Access
A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells
Individual human epidermal cells differ in their self-renewal ability. Here the authors perform genome-wide pooled RNAi screens to uncover the molecular basis for this heterogeneity, and identify genes conferring a clonal growth advantage on normal and neoplastic human epidermal cells.
- Gernot Walko
- , Samuel Woodhouse
- & Fiona M. Watt
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Article
| Open Access
Cell division orientation is coupled to cell–cell adhesion by the E-cadherin/LGN complex
Cell–cell adhesion and oriented cell division play key roles in tissue architecture, but how they are coordinated is not known. Here, the authors show that E-cadherin interacts with LGN, and thereby provides a cortical cue that serves to stabilize cortical attachment of astral microtubules at cell–cell adhesions, thus orienting the mitotic spindle.
- Martijn Gloerich
- , Julie M. Bianchini
- & W. James Nelson
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| Open Access
p120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis
The tumour suppressor p120-catenin (p120) controls cadherin-based adhesion. Here, the authors demonstrate that p120 regulates cytokinesis through binding to the centralspindlin component MKLP1 and controls RhoA activity. Loss of p120 in cancer induces multinucleation and chromosomal instability, independent of cell-cell adhesion.
- Robert A.H. van de Ven
- , Jolien S. de Groot
- & Patrick W.B. Derksen
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| Open Access
Plexins function in epithelial repair in both Drosophila and zebrafish
Plexins are semaphorin receptors and are well known for their roles in neuronal pathfinding. Here the authors describe a role for Plexin A in healing damaged epithelia in Drosophila and zebrafish. In Drosophila, Plexin A inhibits the GTPase Rap1 to allow epithelial remodelling to facilitate wound repair.
- Sa Kan Yoo
- , Heath G. Pascoe
- & Iswar K. Hariharan
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Article
| Open Access
The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions
Cell-cell adhesion of endothelial tissue, mediated by the adhesion molecule VE-cadherin, is tightly regulated. Here the authors show that the F-BAR domain protein pacsin2 is recruited to the trailing end of mechanically unbalanced Focal Adherens Junctions, where it inhibits internalization of VE-cadherin and protects cell-cell adhesion.
- Yvonne L. Dorland
- , Tsveta S. Malinova
- & Stephan Huveneers
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Article
| Open Access
Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension
The stability of epithelial adherens junctions depends on tension generated by actomyosin contractility. Here Lee et al. describe a novel role for the axon guidance receptor Neogenin in maintaining junctional stability by recruiting actin nucleation machinery to adherens junctions.
- Natalie K. Lee
- , Ka Wai Fok
- & Helen M. Cooper
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| Open Access
VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread
Signals through VEGF receptor 2 (VEGFR2) increase vascular permeability, promoting cancer progression. Here the authors show that a point mutation in VEGFR2 preventing its auto-phosphorylation leads to reduced metastatic spread and improved response to chemotherapy in tumor-bearing mice, without affecting tumor inflammation.
- Xiujuan Li
- , Narendra Padhan
- & Lena Claesson-Welsh
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Article
| Open Access
Three mechanisms control E-cadherin localization to the zonula adherens
E-cadherin is an adhesion molecule mediating cell-cell adhesion; correct localization is important but how localization is controlled is not clear. Here the authors use Drosophilaas a model system to distinguish three distinct trafficking pathways that direct E-cadherin to the zonula adherens.
- Innokenty Woichansky
- , Carlo Antonio Beretta
- & Veit Riechmann
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| Open Access
Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo
Vascular endothelial-cadherin is a junctional protein implicated in the control of vascular permeability. Orsenigo et al.find that vascular endothelial-cadherin is phosphorylated in veins but not in arteries of mice, and that this sensitizes vessels to rapid changes in permeability in response to inflammatory mediators.
- Fabrizio Orsenigo
- , Costanza Giampietro
- & Elisabetta Dejana
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Cadherin selectivity filter regulates endothelial sieving properties
Endothelial cells provide a vital barrier system to the passage of water and ions but not large plasma proteins. Using fluorescently labelled dextrans, the authors show that regions of high or low adherens junction density differentially restrict the passage of molecules up to 70 kDa in size.
- Sadiqa K. Quadri
- , Li Sun
- & Jahar Bhattacharya
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Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche
Studying the physical interaction of stem cells with their niche has previously been difficult. Using a fluorescence-based reporter, Michelet al. are able to show that bone morphogenetic protein signalling occurs between Drosophilatestes germline stem cells and their niche and is via adherens junctions.
- Marcus Michel
- , Isabel Raabe
- & Christian Bökel
Ubiquitin ligase CHFR mediated degradation of VE-cadherin through ubiquitylation disrupts endothelial adherens junctions