How cells tell up from down and stick together to construct multicellular tissues – interplay between apicobasal polarity and cell–cell adhesion

2021 ◽  
Vol 134 (21) ◽  
Author(s):  
Claudia G. Vasquez ◽  
Eva L. de la Serna ◽  
Alexander R. Dunn

ABSTRACT Polarized epithelia define a topological inside and outside, and hence constitute a key evolutionary innovation that enabled the construction of complex multicellular animal life. Over time, this basic function has been elaborated upon to yield the complex architectures of many of the organs that make up the human body. The two processes necessary to yield a polarized epithelium, namely regulated adhesion between cells and the definition of the apicobasal (top–bottom) axis, have likewise undergone extensive evolutionary elaboration, resulting in multiple sophisticated protein complexes that contribute to both functions. Understanding how these components function in combination to yield the basic architecture of a polarized cell–cell junction remains a major challenge. In this Review, we introduce the main components of apicobasal polarity and cell–cell adhesion complexes, and outline what is known about their regulation and assembly in epithelia. In addition, we highlight studies that investigate the interdependence between these two networks. We conclude with an overview of strategies to address the largest and arguably most fundamental unresolved question in the field, namely how a polarized junction arises as the sum of its molecular parts.

2019 ◽  
Vol 30 (16) ◽  
pp. 1930-1937 ◽  
Author(s):  
Si Ming Pang ◽  
Shimin Le ◽  
Adam V. Kwiatkowski ◽  
Jie Yan

αT (Testes)-catenin, a critical factor regulating cell–cell adhesion in the heart, directly couples the cadherin-catenin complex to the actin cytoskeleton at the intercalated disk (ICD), a unique cell–cell junction that couples cardiomyocytes. Loss of αT-catenin in mice reduces plakophilin2 and connexin 43 recruitment to the ICD. Since αT-catenin is subjected to mechanical stretch during actomyosin contraction in cardiomyocytes, its activity could be regulated by mechanical force. To provide insight in how force regulates αT-catenin function, we investigated the mechanical stability of the putative, force-sensing middle (M) domain of αT-catenin and determined how force impacts vinculin binding to αT-catenin. We show that 1) physiological levels of force, <15 pN, are sufficient to unfold the three M domains; 2) the M1 domain that harbors the vinculin-binding site is unfolded at ∼6 pN; and 3) unfolding of the M1 domain is necessary for high-affinity vinculin binding. In addition, we quantified the binding kinetics and affinity of vinculin to the mechanically exposed binding site in M1 and observed that αT-catenin binds vinculin with low nanomolar affinity. These results provide important new insights into the mechanosensing properties of αT-catenin and how αT-catenin regulates cell–cell adhesion at the cardiomyocyte ICD.


2010 ◽  
Vol 191 (4) ◽  
pp. 761-769 ◽  
Author(s):  
Ronen Zaidel-Bar ◽  
Michael J. Joyce ◽  
Allison M. Lynch ◽  
Kristen Witte ◽  
Anjon Audhya ◽  
...  

Robust cell–cell adhesion is critical for tissue integrity and morphogenesis, yet little is known about the molecular mechanisms controlling cell–cell junction architecture and strength. We discovered that SRGP-1 is a novel component of cell–cell junctions in Caenorhabditis elegans, localizing via its F-BAR (Bin1, Amphiphysin, and RVS167) domain and a flanking 200–amino acid sequence. SRGP-1 activity promotes an increase in membrane dynamics at nascent cell–cell contacts and the rapid formation of new junctions; in addition, srgp-1 loss of function is lethal in embryos with compromised cadherin–catenin complexes. Conversely, excess SRGP-1 activity leads to outward bending and projections of junctions. The C-terminal half of SRGP-1 interacts with the N-terminal F-BAR domain and negatively regulates its activity. Significantly, in vivo structure–function analysis establishes a role for the F-BAR domain in promoting rapid and robust cell adhesion during embryonic closure events, independent of the Rho guanosine triphosphatase–activating protein domain. These studies establish a new role for this conserved protein family in modulating cell–cell adhesion.


2021 ◽  
Vol 118 (7) ◽  
pp. e2019347118
Author(s):  
Amir Monemian Esfahani ◽  
Jordan Rosenbohm ◽  
Bahareh Tajvidi Safa ◽  
Nickolay V. Lavrik ◽  
Grayson Minnick ◽  
...  

Cell–cell adhesions are often subjected to mechanical strains of different rates and magnitudes in normal tissue function. However, the rate-dependent mechanical behavior of individual cell–cell adhesions has not been fully characterized due to the lack of proper experimental techniques and therefore remains elusive. This is particularly true under large strain conditions, which may potentially lead to cell–cell adhesion dissociation and ultimately tissue fracture. In this study, we designed and fabricated a single-cell adhesion micro tensile tester (SCAµTT) using two-photon polymerization and performed displacement-controlled tensile tests of individual pairs of adherent epithelial cells with a mature cell–cell adhesion. Straining the cytoskeleton–cell adhesion complex system reveals a passive shear-thinning viscoelastic behavior and a rate-dependent active stress-relaxation mechanism mediated by cytoskeleton growth. Under low strain rates, stress relaxation mediated by the cytoskeleton can effectively relax junctional stress buildup and prevent adhesion bond rupture. Cadherin bond dissociation also exhibits rate-dependent strengthening, in which increased strain rate results in elevated stress levels at which cadherin bonds fail. This bond dissociation becomes a synchronized catastrophic event that leads to junction fracture at high strain rates. Even at high strain rates, a single cell–cell junction displays a remarkable tensile strength to sustain a strain as much as 200% before complete junction rupture. Collectively, the platform and the biophysical understandings in this study are expected to build a foundation for the mechanistic investigation of the adaptive viscoelasticity of the cell–cell junction.


F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 550 ◽  
Author(s):  
Olga Klezovitch ◽  
Valeri Vasioukhin

Cadherin-catenin complexes are critical for the assembly of cell-cell adhesion structures known as adherens junctions. In addition to the mechanical linkage of neighboring cells to each other, these cell-cell adhesion protein complexes have recently emerged as important sensors and transmitters of the extracellular cues inside the cell body and into the nucleus. In the past few years, multiple studies have identified a connection between the cadherin-catenin protein complexes and major intracellular signaling pathways. Those studies are the main focus of this review.


2003 ◽  
Vol 14 (10) ◽  
pp. 4207-4220 ◽  
Author(s):  
Philipp Alberts ◽  
Rachel Rudge ◽  
Ina Hinners ◽  
Aude Muzerelle ◽  
Sonia Martinez-Arca ◽  
...  

The membrane-trafficking pathway mediated by tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) in neurons is still unknown. We show herein that TI-VAMP expression is necessary for neurite outgrowth in PC12 cells and hippocampal neurons in culture. TI-VAMP interacts with plasma membrane and endosomal target soluble N-ethylmaleimide-sensitive factor attachment protein receptors, suggesting that TI-VAMP mediates a recycling pathway. L1, a cell-cell adhesion molecule involved in axonal outgrowth, colocalized with TI-VAMP in the developing brain, neurons in culture, and PC12 cells. Plasma membrane L1 was internalized into the TI-VAMP–containing compartment. Silencing of TI-VAMP resulted in reduced expression of L1 at the plasma membrane. Finally, using the extracellular domain of L1 and N-cadherin immobilized on beads, we found that the silencing of TI-VAMP led to impaired L1- but not N-cadherin–mediated adhesion. Furthermore, TI-VAMP- but not synaptobrevin 2-containing vesicles accumulated at the site of the L1 bead-cell junction. We conclude that TI-VAMP mediates the intracellular transport of L1 and that L1-mediated adhesion controls this membrane trafficking, thereby suggesting an important cross talk between membrane trafficking and cell-cell adhesion.


2018 ◽  
Author(s):  
Vanesa Jiménez-Amilburu ◽  
Didier Y.R. Stainier

AbstractTissue morphogenesis requires changes in cell-cell adhesion as well as in cell shape and polarity. Cardiac trabeculation is a morphogenetic process essential to form a functional ventricular wall. Here we show that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, display compact wall integrity defects and fail to form trabeculae. Crb2a localization is very dynamic, at a time when other cardiomyocyte junctional proteins also relocalize. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a is expressed in all ventricular cardiomyocytes colocalizing with the junctional protein ZO-1. Subsequently, Crb2a becomes localized all along the apical membrane of compact layer cardiomyocytes and is downregulated by those delaminating. We show that blood flow and Nrg/ErbB2 signaling regulate these Crb2a localization changes. crb2a mutants display a multilayered wall with polarized cardiomyocytes, a unique phenotype. Our data further indicate that Crb2a regulates cardiac trabeculation by controlling the localization of tight and adherens junctions in cardiomyocytes. Importantly, transplantation data show that Crb2a controls trabeculation in a CM-autonomous manner. Altogether, our study reveals a critical role for Crb2a during cardiac development.Summary statementInvestigation of the Crumbs polarity protein Crb2a in zebrafish reveals a novel role in cardiac development via regulation of cell-cell adhesion and apicobasal polarity.


2005 ◽  
Vol 173 (4S) ◽  
pp. 170-170
Author(s):  
Maxine G. Tran ◽  
Miguel A. Esteban ◽  
Peter D. Hill ◽  
Ashish Chandra ◽  
Tim S. O'Brien ◽  
...  

Author(s):  
Martha Ivanivna Karpa

The article reveals the main features of the competence approach in the practice of European public administration. The features of the competence approach in public administration are determined on the basis of analysis of the basic concepts of public administration. In the dynamics of the formation and development of popular theories of interaction between state and local authorities, such as the theory of a free community, community (public) and public and state (the theory of municipal dualism), we can trace a number of characteristic features of a competency approach, which manifests itself both through the general theoretical relations and manifestations, and through the practice of coexistence of public authorities. There is a problem of definition and distribution of public functions as a prerequisite for defining and shaping the competences of public institutions. An important issue in the context of a competent approach is the institutional consolidation of functions in the context of the existence of the basic models of territorial organization of power. In each of the varieties of the Governance concept (Responsive Governance concept, Democratic Governance concept, Good Governance concept), the specifics of the use of competencies are defined. The archetypal symbols in the European public administration are singled out using the analysis of competence in public administration in its main constituents. A brief description of the archetypal aspect of European public administration is given. The main components of competence are shown in connection with the existing archetypal symbols and the characteristic trends of their development. Their connection is shown according to the scheme “the entity component (who?) — the object component (what?) — the administrative component (how?) — the basis (in what environment?)”. Concerning the trends of development of a competence approach in the context of practice and theory of public administration, it is determined that modern concepts of public administration are characterized by shifting the balance between state and public institutions to the sphere of common goals and tasks, and thus responsibility. The joint activity of all subjects of society requires new forms of cooperation, definition of the spheres and subjects of each entity’s activity for effective cooperation, distribution of functions and competences of the entities, formation and consolidation of their status characteristics.


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