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Current Topics in Developmental Biology 2015Cell-cell adhesions are necessary for structural integrity and barrier formation of the epidermis. Here, we discuss insights from genetic and cell biological studies... (Review)
Review
Cell-cell adhesions are necessary for structural integrity and barrier formation of the epidermis. Here, we discuss insights from genetic and cell biological studies into the roles of individual cell-cell junctions and their composite proteins in regulating epidermal development and function. In addition to individual adhesive functions, we will discuss emerging ideas on mechanosensation/transduction of junctions in the epidermis, noncanonical roles for adhesion proteins, and crosstalk/interdependencies between the junctional systems. These studies have revealed that cell adhesion proteins are connected to many aspects of tissue physiology including growth control, differentiation, and inflammation.
Topics: Adherens Junctions; Animals; Cell Adhesion; Cell Adhesion Molecules; Cell Differentiation; Epidermal Cells; Epidermis; Humans; Signal Transduction
PubMed: 25733147
DOI: 10.1016/bs.ctdb.2014.11.027 -
Nature Reviews. Molecular Cell Biology Apr 2024Tissue and organ development during embryogenesis relies on the collective and coordinated action of many cells. Recent studies have revealed that tissue material... (Review)
Review
Tissue and organ development during embryogenesis relies on the collective and coordinated action of many cells. Recent studies have revealed that tissue material properties, including transitions between fluid and solid tissue states, are controlled in space and time to shape embryonic structures and regulate cell behaviours. Although the collective cellular flows that sculpt tissues are guided by tissue-level physical changes, these ultimately emerge from cellular-level and subcellular-level molecular mechanisms. Adherens junctions are key subcellular structures, built from clusters of classical cadherin receptors. They mediate physical interactions between cells and connect biochemical signalling to the physical characteristics of cell contacts, hence playing a fundamental role in tissue morphogenesis. In this Review, we take advantage of the results of recent, quantitative measurements of tissue mechanics to relate the molecular and cellular characteristics of adherens junctions, including adhesion strength, tension and dynamics, to the emergent physical state of embryonic tissues. We focus on systems in which cell-cell interactions are the primary contributor to morphogenesis, without significant contribution from cell-matrix interactions. We suggest that emergent tissue mechanics is an important direction for future research, bridging cell biology, developmental biology and mechanobiology to provide a holistic understanding of morphogenesis in health and disease.
Topics: Adherens Junctions; Cadherins; Cell Communication; Morphogenesis; Embryonic Development; Cell Adhesion
PubMed: 38093099
DOI: 10.1038/s41580-023-00688-7 -
Seminars in Cell & Developmental Biology Dec 2014Epithelial cells form regulated and selective barriers between distinct tissue compartments. The Apical Junctional Complex (AJC) consisting of the tight junction (TJ)... (Review)
Review
Epithelial cells form regulated and selective barriers between distinct tissue compartments. The Apical Junctional Complex (AJC) consisting of the tight junction (TJ) and adherens junction (AJ) control epithelial homeostasis, paracellular permeability and barrier properties. The AJC is composed of mutliprotein complexes consisting of transmembrane proteins that affiliate with an underlying perijunctional F-actin myosin ring through cytoplasmic scaffold proteins. AJC protein associations with the apical actin-myosin cytoskeleton are tightly controlled by a number of signaling proteins including the Rho family of GTPases that orchestrate junctional biology, epithelial homeostasis and barrier function. This review highlights the vital relationship of Rho GTPases and AJCs in controlling the epithelial barrier. The pathophysiologic relationship of Rho GTPases, AJC, apical actomyosin cytoskeleton and epithelial barrier function is discussed.
Topics: Actin Cytoskeleton; Actins; Actomyosin; Adherens Junctions; Epithelial Cells; Humans; Myosins; Permeability; Signal Transduction; Tight Junctions; rho GTP-Binding Proteins
PubMed: 25223584
DOI: 10.1016/j.semcdb.2014.09.003 -
Biophysical Journal Mar 2022Cadherin-based adherens junctions and desmosomes help stabilize cell-cell contacts with additional function in mechano-signaling, while clustered protocadherin junctions...
Cadherin-based adherens junctions and desmosomes help stabilize cell-cell contacts with additional function in mechano-signaling, while clustered protocadherin junctions are responsible for directing neuronal circuits assembly. Structural models for adherens junctions formed by epithelial cadherin (CDH1) proteins indicate that their long, curved ectodomains arrange to form a periodic, two-dimensional lattice stabilized by tip-to-tip trans interactions (across junction) and lateral cis contacts. Less is known about the exact architecture of desmosomes, but desmoglein (DSG) and desmocollin (DSC) cadherin proteins are also thought to form ordered junctions. In contrast, clustered protocadherin (PCDH)-based cell-cell contacts in neuronal tissues are thought to be responsible for self-recognition and avoidance, and structural models for clustered PCDH junctions show a linear arrangement in which their long and straight ectodomains form antiparallel overlapped trans complexes. Here, we report all-atom molecular dynamics simulations testing the mechanics of minimalistic adhesive junctions formed by CDH1, DSG2 coupled to DSC1, and PCDHγB4, with systems encompassing up to 3.7 million atoms. Simulations generally predict a favored shearing pathway for the adherens junction model and a two-phased elastic response to tensile forces for the adhesive adherens junction and the desmosome models. Complexes within these junctions first unbend at low tensile force and then become stiff to unbind without unfolding. However, cis interactions in both the CDH1 and DSG2-DSC1 systems dictate varied mechanical responses of individual dimers within the junctions. Conversely, the clustered protocadherin PCDHγB4 junction lacks a distinct two-phased elastic response. Instead, applied tensile force strains trans interactions directly, as there is little unbending of monomers within the junction. Transient intermediates, influenced by new cis interactions, are observed after the main rupture event. We suggest that these collective, complex mechanical responses mediated by cis contacts facilitate distinct functions in robust cell-cell adhesion for classical cadherins and in self-avoidance signaling for clustered PCDHs.
Topics: Adherens Junctions; Cadherins; Cell Adhesion; Cell Communication
PubMed: 35150618
DOI: 10.1016/j.bpj.2022.02.008 -
International Journal of Molecular... Jul 2018Cell contacts exhibit a considerable influence on tissue physiology and homeostasis by controlling paracellular and intercellular transport processes, as well as by... (Review)
Review
Cell contacts exhibit a considerable influence on tissue physiology and homeostasis by controlling paracellular and intercellular transport processes, as well as by affecting signaling pathways. Since they maintain cell polarity, they play an important role in cell plasticity. The knowledge about the junctional protein families and their interactions has increased considerably during recent years. In contrast to most other tissues, the endometrium undergoes extensive physiological changes and reveals an extraordinary plasticity due to its crucial role in the establishment and maintenance of pregnancy. These complex changes are accompanied by changes in direct cell⁻cell contacts to meet the various requirements in the respective developmental stage. Impairment of this sophisticated differentiation process may lead to failure of implantation and embryo development and may be involved in the pathogenesis of endometrial diseases. In this article, we focus on the knowledge about the distribution and regulation of the different junctional proteins in the endometrium during cycling and pregnancy, as well as in pathologic conditions such as endometriosis and cancer. Decoding these sophisticated interactions should improve our understanding of endometrial physiology as well as of the mechanisms involved in pathological conditions.
Topics: Adherens Junctions; Animals; Cell Communication; Embryo Implantation; Endometrial Neoplasms; Endometriosis; Endometrium; Female; Hormones; Humans; Tight Junctions
PubMed: 30061539
DOI: 10.3390/ijms19082227 -
Cold Spring Harbor Perspectives in... Nov 2018Cadherin-based adherens junctions (AJs) and desmosomes are crucial to couple intercellular adhesion to the actin or intermediate filament cytoskeletons, respectively. As... (Review)
Review
Cadherin-based adherens junctions (AJs) and desmosomes are crucial to couple intercellular adhesion to the actin or intermediate filament cytoskeletons, respectively. As such, these intercellular junctions are essential to provide not only integrity to epithelia and other tissues but also the mechanical machinery necessary to execute complex morphogenetic and homeostatic intercellular rearrangements. Moreover, these spatially defined junctions serve as signaling hubs that integrate mechanical and chemical pathways to coordinate tissue architecture with behavior. This review takes an evolutionary perspective on how the emergence of these two essential intercellular junctions at key points during the evolution of multicellular animals afforded metazoans with new opportunities to integrate adhesion, cytoskeletal dynamics, and signaling. We discuss known literature on cross-talk between the two junctions and, using the skin epidermis as an example, provide a model for how these two junctions function in concert to orchestrate tissue organization and function.
Topics: Adherens Junctions; Animals; Biological Evolution; Cell Polarity; Desmosomes; Epithelial Cells; Signal Transduction
PubMed: 28893859
DOI: 10.1101/cshperspect.a029207 -
Cold Spring Harbor Perspectives in... Mar 2017Cadherin-based adherens junctions are conserved structures that mediate epithelial cell-cell adhesion in invertebrates and vertebrates. Despite their pivotal function in... (Review)
Review
Cadherin-based adherens junctions are conserved structures that mediate epithelial cell-cell adhesion in invertebrates and vertebrates. Despite their pivotal function in epithelial integrity, adherens junctions show a remarkable plasticity that is a prerequisite for tissue architecture and morphogenesis. Epithelial cadherin (E-cadherin) is continuously turned over and undergoes cycles of endocytosis, sorting and recycling back to the plasma membrane. Mammalian cell culture and genetically tractable model systems such as have revealed conserved, but also distinct, mechanisms in the regulation of E-cadherin membrane trafficking. Here, we discuss our current knowledge about molecules and mechanisms controlling endocytosis, sorting and recycling of E-cadherin during junctional remodeling.
Topics: Adherens Junctions; Animals; Biological Transport; Cadherins; Catenins; Endocytosis; Endosomes; Protein Processing, Post-Translational
PubMed: 28096264
DOI: 10.1101/cshperspect.a029140 -
Cardiovascular Research Mar 2017This review presents an extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes.... (Review)
Review
This review presents an extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes. Classically, three main structures are distinguished: gap junctions (GJs) metabolically and electrically connect cytoplasm of adjacent cardiomyocytes; adherens junctions (AJs) connect the actin cytoskeleton of adjacent cells; and desmosomes function as cell anchors and connect intermediate filaments. Furthermore, ion channels reside in the ID. Mutations in ID proteins have been associated with cardiac arrhythmias such as Brugada syndrome and arrhythmogenic cardiomyopathy. However, rather than being independent, all ID components work together intensively by multifunctional proteins such as ZO-1, Ankyrin G, and β-catenin, integrating mechanical and electrical functions. GJs form a plaque surrounded by the perinexus in which free connexons reside; the connexome integrates NaV channels, the desmosome and GJs; and the area composita hosts AJs and desmosomes, also integrated as adhering junctions. Furthermore, the transitional junction connects sarcomeres to the plasma membrane. Lastly, this review integrates all these findings in comprehensible figures, illustrating the interdependencies of ID proteins.
Topics: Adherens Junctions; Animals; Arrhythmias, Cardiac; Cell Communication; Desmosomes; Gap Junctions; Genetic Predisposition to Disease; Humans; Intercellular Junctions; Ion Channels; Mechanotransduction, Cellular; Membrane Proteins; Mutation; Myocytes, Cardiac; Signal Transduction
PubMed: 28069669
DOI: 10.1093/cvr/cvw259 -
Cell Reports Aug 2020Entosis is a cell-in-cell (CIC)-mediated death program. Contractile actomyosin (CA) and the adherens junction (AJ) are two core elements essential for entotic CIC...
Entosis is a cell-in-cell (CIC)-mediated death program. Contractile actomyosin (CA) and the adherens junction (AJ) are two core elements essential for entotic CIC formation, but the molecular structures interfacing them remain poorly understood. Here, we report the characterization of a ring-like structure interfacing between the peripheries of invading and engulfing cells. The ring-like structure is a multi-molecular complex consisting of adhesive and cytoskeletal proteins, in which the mechanical sensor vinculin is highly enriched. The vinculin-enriched structure senses mechanical force imposed on cells, as indicated by fluorescence resonance energy transfer (FRET) analysis, and is thus termed the mechanical ring (MR). The MR actively interacts with CA and the AJ to help establish and maintain polarized actomyosin that drives cell internalization. Vinculin depletion leads to compromised MR formation, CA depolarization, and subsequent CIC failure. In summary, we suggest that the vinculin-enriched MR, in addition to CA and AJ, is another core element essential for entosis.
Topics: Actomyosin; Adherens Junctions; Cell Death; Cell-in-Cell Formation; Entosis; Humans
PubMed: 32846129
DOI: 10.1016/j.celrep.2020.108071 -
Journal of Biochemistry Nov 2019Ether glycerolipids, plasmalogens are found in various mammalian cells and tissues. However, physiological role of plasmalogens in epithelial cells remains unknown. We...
Ether glycerolipids, plasmalogens are found in various mammalian cells and tissues. However, physiological role of plasmalogens in epithelial cells remains unknown. We herein show that synthesis of ethanolamine-containing plasmalogens, plasmenylethanolamine (PlsEtn), is deficient in MCF7 cells, an epithelial cell line, with severely reduced expression of alkyl-dihydroxyacetonephosphate synthase (ADAPS), the second enzyme in the PlsEtn biosynthesis. Moreover, expression of ADAPS or supplementation of PlsEtn containing C18-alkenyl residue delays the migration of MCF7 cells as compared to that mock-treated MCF7 and C16-alkenyl-PlsEtn-supplemented MCF7 cells. Localization of E-cadherin to cell-cell junctions is highly augmented in cells containing C18-alkenyl-PlsEtn. Together, these results suggest that PlsEtn containing C18-alkenyl residue plays a distinct role in the integrity of E-cadherin-mediated adherens junction.
Topics: Adherens Junctions; Humans; MCF-7 Cells; Plasmalogens; Tumor Cells, Cultured
PubMed: 31236591
DOI: 10.1093/jb/mvz049