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Traffic (Copenhagen, Denmark) Dec 2016Cadherins are the primary adhesion molecules in adherens junctions and desmosomes and play essential roles in embryonic development. Although significant progress has... (Review)
Review
Cadherins are the primary adhesion molecules in adherens junctions and desmosomes and play essential roles in embryonic development. Although significant progress has been made in understanding cadherin structure and function, we lack a clear vision of how cells confer plasticity upon adhesive junctions to allow for cellular rearrangements during development, wound healing and metastasis. Endocytic membrane trafficking has emerged as a fundamental mechanism by which cells confer a dynamic state to adhesive junctions. Recent studies indicate that the juxtamembrane domain of classical cadherins contains multiple endocytic motifs, or "switches," that can be used by cellular membrane trafficking machinery to regulate adhesion. The cadherin-binding protein p120-catenin (p120) appears to be the master regulator of access to these switches, thereby controlling cadherin endocytosis and turnover. This review focuses on p120 and other cadherin-binding proteins, ubiquitin ligases, and growth factors as key modulators of cadherin membrane trafficking.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Cell Membrane; Embryonic Development; Endocytosis; Humans; Protein Transport
PubMed: 27624909
DOI: 10.1111/tra.12448 -
FEBS Letters Jan 2022The apical junctional complex (AJC) is a membrane protein ultrastructure that regulates cell adhesion and homeostasis. The tight junction (TJ) and the adherens junction...
The apical junctional complex (AJC) is a membrane protein ultrastructure that regulates cell adhesion and homeostasis. The tight junction (TJ) and the adherens junction (AJ) are substructures of the AJC. The interplay between TJ and AJ membrane proteins to assemble the AJC remains unclear. We employed synthetic biology strategies to express the basic membrane elements of a simple AJC-the adhesive extracellular domains of junctional adhesion molecule A (JAM-A), epithelial cadherin, claudin 1, and occludin-to study their interactions. Our results suggest that calcium concentration fluctuations and JAM-A, acting as an interface molecule between the TJ and AJ, orchestrate their interplay. Calcium affects the secondary structure, oligomerization, and binding affinity of homotypic and heterotypic interactions of TJ and AJ components, thus acting as a molecular switch influencing AJC dynamics.
Topics: Adherens Junctions
PubMed: 34882783
DOI: 10.1002/1873-3468.14252 -
Frontiers in Bioscience (Landmark... Jan 2009The activity of E-cadherin-adhesion complexes is under stringent control of signaling pathways. Conversely, these adhesion complexes are preferential sites for signal... (Review)
Review
The activity of E-cadherin-adhesion complexes is under stringent control of signaling pathways. Conversely, these adhesion complexes are preferential sites for signal transduction. One class of signaling molecules reported to regulate adherens junction and to be activated by adherens junction assembly are phosphatidylinositol 3-kinases. While the exact molecular mechanisms involved are not clear, present data indicate that one of the earliest events likely involves c-Src which is rapidly activated by E-cadherin-mediated cellular aggregation and may facilitate the recruitment and activation of PI3K to E-cadherin-containing complexes. Beta-catenin, gamma-catenin and hDlg which are present at cell-cell adhesions can act as docking proteins for PI3K. Hence, cell-cell interaction leads to PtdIns(3,4,5)P3 production in nascent cadherin contacts triggering the recruitment of proteins containing pleckstrin homology domains including the kinase PKB/Akt and the exchange factors for Rac, Tiam and Vav. PKB/Akt may be involved in the regulation of survival and proliferation while Tiam and Vav may activate Rac, resulting in reorganization of actin cytoskeleton which ultimately serves to mediate adhesive cell-cell recognition as well as epithelial cell differentiation and polarity.
Topics: Adherens Junctions; Animals; Cadherins; Cell Communication; Cell Differentiation; Cell Polarity; Epithelial Cells; Humans; Phosphatidylinositol 3-Kinases
PubMed: 19273082
DOI: 10.2741/3259 -
Cold Spring Harbor Perspectives in... Feb 2010Intercellular anchoring junctions are highly specialized regions of the plasma membrane where members of the cadherin family of transmembrane adhesion molecules on... (Review)
Review
Intercellular anchoring junctions are highly specialized regions of the plasma membrane where members of the cadherin family of transmembrane adhesion molecules on opposing cells interact through their extracellular domains, and through their cytoplasmic domains serve as a platform for organizing cytoskeletal anchors and remodelers. Here we focus on assembly of so-called "anchoring" or "adhering" junctions-adherens junctions (AJs) and desmosomes (DSMs), which associate with actin and intermediate filaments, respectively. We will examine how the assembly and function of AJs and DSMs are intimately connected during embryogenesis and in adult cells and tissues, and in some cases even form specialized "mixed" junctions. We will explore signaling and trafficking machineries that drive assembly and remodeling and how these mechanisms are co-opted in human disease.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Cell Membrane; Cytoskeleton; Desmosomes; Endocytosis; Homeostasis; Humans; Intercellular Junctions; Intermediate Filaments; Models, Biological
PubMed: 20182611
DOI: 10.1101/cshperspect.a000125 -
Sub-cellular Biochemistry 2012Caenorhabditis elegans provides a simplified, in vivo model system in which to study adherens junctions (AJs) and their role in morphogenesis. The core AJ... (Review)
Review
Caenorhabditis elegans provides a simplified, in vivo model system in which to study adherens junctions (AJs) and their role in morphogenesis. The core AJ components-HMR-1/E-cadherin, HMP-2/β-catenin and HMP-1/α-catenin-were initially identified through genetic screens for mutants with body axis elongation defects. In early embryos, AJ proteins are found at sites of contact between blastomeres, and in epithelial cells AJ proteins localize to the multifaceted apical junction (CeAJ)-a single structure that combines the adhesive and barrier functions of vertebrate adherens and tight junctions. The apically localized polarity proteins PAR-3 and PAR-6 mediate formation and maturation of junctions, while the basolaterally localized regulator LET-413/Scribble ensures that junctions remain apically positioned. AJs promote robust adhesion between epithelial cells and provide mechanical resistance for the physical strains of morphogenesis. However, in contrast to vertebrates, C. elegans AJ proteins are not essential for general cell adhesion or for epithelial cell polarization. A combination of conserved and novel proteins localizes to the CeAJ and works together with AJ proteins to mediate adhesion.
Topics: Adherens Junctions; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Morphogenesis
PubMed: 22674076
DOI: 10.1007/978-94-007-4186-7_12 -
Cell Adhesion & Migration 2014The endothelium forms a selective semi-permeable barrier controlling bidirectional transfer between blood vessel and irrigated tissues. This crucial function relies on... (Review)
Review
The endothelium forms a selective semi-permeable barrier controlling bidirectional transfer between blood vessel and irrigated tissues. This crucial function relies on the dynamic architecture of endothelial cell–cell junctions, and in particular, VE -cadherin-mediated contacts. VE -cadherin indeed chiefly organizes the opening and closing of the endothelial barrier, and is central in permeability changes. In this review, the way VE -cadherin-based contacts are formed and maintained is first presented, including molecular traits of its expression, partners, and signaling. In a second part, the mechanisms by which VE -cadherin adhesion can be disrupted, leading to cell–cell junction weakening and endothelial permeability increase, are described. Overall, the molecular basis for VE -cadherin control of the endothelial barrier function is of high interest for biomedical research, as vascular leakage is observed in many pathological conditions and human diseases.
Topics: Adherens Junctions; Antigens, CD; Cadherins; Capillary Permeability; Cell Communication; Endothelial Cells; Humans; Signal Transduction; Tight Junctions; Vascular Endothelial Growth Factor A; beta Catenin
PubMed: 25422846
DOI: 10.4161/cam.29026 -
Cell Communication & Adhesion Jun 2014Intercellular adhesive junctions are essential for maintaining the physical integrity of tissues; this is particularly true for the heart that is under constant... (Review)
Review
Intercellular adhesive junctions are essential for maintaining the physical integrity of tissues; this is particularly true for the heart that is under constant mechanical load. The correct functionality of the heart is dependent on the electrical and mechanical coordination of its constituent cardiomyocytes. The intercalated disc (ID) structure located at the termini of the rod-shaped adult cardiomyocyte contains various junctional proteins responsible for the integration of structural information and cell-cell communication. According to the classical description, the ID consists of three distinct junctional complexes: adherens junction (AJ), desmosome (Des), and gap junction (GJ) that work together to mediate mechanical and electrical coupling of cardiomyocytes. However, recent morphological and molecular studies indicate that AJ and Des components are capable of mixing together resulting in a "hybrid adhering junction" or "area composita." This review summarizes recent progress in understanding the in vivo function(s) of AJ components in cardiac homeostasis and disease.
Topics: Adherens Junctions; Animals; Cadherins; Catenins; Humans; Myocytes, Cardiac
PubMed: 24766605
DOI: 10.3109/15419061.2014.908853 -
Traffic (Copenhagen, Denmark) Dec 2016Cadherin-based adherens junctions are critical for connecting cells in tissues. Regulated cadherin trafficking also makes these complexes amazingly dynamic, with... (Review)
Review
Cadherin-based adherens junctions are critical for connecting cells in tissues. Regulated cadherin trafficking also makes these complexes amazingly dynamic, with permissive and instructive consequences on multicellular development. Here, we review how cadherin trafficking affects various forms of tissue morphogenesis from Drosophila and Caenorhabditis elegans to zebrafish, Xenopus and mouse. We describe how core trafficking machinery (such as clathrin, dynamin, Rab small G proteins and the exocyst complex) integrates with other molecular systems (transcriptional factors, signaling pathways, microtubules, actin networks, apico-basal polarity proteins and planar cell polarity proteins) to control cadherin endocytosis, exocytosis and recycling. This control can occur at all cell-cell contacts or specific junctions for distinct effects on tissue morphogenesis during animal development.
Topics: Adherens Junctions; Animals; Cadherins; Cell Polarity; Embryonic Development; Endocytosis; Exocytosis; Humans; Morphogenesis; Organogenesis; Protein Transport
PubMed: 27105637
DOI: 10.1111/tra.12407 -
The Journal of Biological Chemistry Nov 2019To perceive their three-dimensional environment, cells and tissues must be able to sense and interpret various physical forces like shear, tensile, and compression... (Review)
Review
To perceive their three-dimensional environment, cells and tissues must be able to sense and interpret various physical forces like shear, tensile, and compression stress. These forces can be generated both internally and externally in response to physical properties, like substrate stiffness, cell contractility, and forces generated by adjacent cells. Mechanical cues have important roles in cell fate decisions regarding proliferation, survival, and differentiation as well as the processes of tissue regeneration and wound repair. Aberrant remodeling of the extracellular space and/or defects in properly responding to mechanical cues likely contributes to various disease states, such as fibrosis, muscle diseases, and cancer. Mechanotransduction involves the sensing and translation of mechanical forces into biochemical signals, like activation of specific genes and signaling cascades that enable cells to adapt to their physical environment. The signaling pathways involved in mechanical signaling are highly complex, but numerous studies have highlighted a central role for the Hippo pathway and other signaling networks in regulating the YAP and TAZ (YAP/TAZ) proteins to mediate the effects of mechanical stimuli on cellular behavior. How mechanical cues control YAP/TAZ has been poorly understood. However, rapid progress in the last few years is beginning to reveal a surprisingly diverse set of pathways for controlling YAP/TAZ. In this review, we will focus on how mechanical perturbations are sensed through changes in the actin cytoskeleton and mechanosensors at focal adhesions, adherens junctions, and the nuclear envelope to regulate YAP/TAZ.
Topics: Actin Cytoskeleton; Adaptor Proteins, Signal Transducing; Adherens Junctions; Animals; Focal Adhesions; Humans; Mechanotransduction, Cellular; Signal Transduction; Trans-Activators; Transcription Factors; Transcriptional Coactivator with PDZ-Binding Motif Proteins; YAP-Signaling Proteins
PubMed: 31594864
DOI: 10.1074/jbc.REV119.007963 -
Trends in Cell Biology Nov 2013Desmosomes are intercellular junctions that anchor intermediate filaments (IFs) to the plasma membrane, forming a supracellular scaffold that provides mechanical... (Review)
Review
Desmosomes are intercellular junctions that anchor intermediate filaments (IFs) to the plasma membrane, forming a supracellular scaffold that provides mechanical resilience to tissues. This anchoring function is accomplished by specialized members of the cadherin family and associated cytoskeletal linking proteins, which together form a highly organized membrane core flanked by mirror-image cytoplasmic plaques. Due to the biochemical insolubility of desmosomes, the mechanisms that govern assembly of these components into a functional organelle remained elusive. Recently developed molecular reporters and live cell imaging approaches have provided powerful new tools to monitor this finely tuned process in real time. Here we discuss studies that are beginning to decipher the machinery and regulation governing desmosome assembly and homeostasis in situ and how these mechanisms are affected during disease pathogenesis.
Topics: Adherens Junctions; Animals; Desmosomes; Homeostasis; Humans
PubMed: 23891292
DOI: 10.1016/j.tcb.2013.06.004