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Trends in Cell Biology May 2023The cell-cell connections in adherens junctions (AJs) are mediated by transmembrane receptors, type I cadherins (referred to here as cadherins). These cadherin-based... (Review)
Review
The cell-cell connections in adherens junctions (AJs) are mediated by transmembrane receptors, type I cadherins (referred to here as cadherins). These cadherin-based connections (or trans bonds) are weak. To upregulate their strength, cadherins exploit avidity, the increased affinity of binding between cadherin clusters compared with isolated monomers. Formation of such clusters is a unique molecular process that is driven by a synergy of direct and indirect cis interactions between cadherins located at the same cell. In addition to their role in adhesion, cadherin clusters provide structural scaffolds for cytosolic proteins, which implicate cadherin into different cellular activities and signaling pathways. The cluster lifetime, which depends on the actin cytoskeleton, and on the mechanical forces it generates, determines the strength of AJs and their plasticity. The key aspects of cadherin adhesion, therefore, cannot be understood at the level of isolated cadherin molecules, but should be discussed in the context of cadherin clusters.
Topics: Humans; Cadherins; Cell Adhesion Molecules; Adherens Junctions; Actins; Actin Cytoskeleton; Cell Adhesion
PubMed: 36127186
DOI: 10.1016/j.tcb.2022.08.007 -
Sub-cellular Biochemistry 2012Classical cadherins are a family of transmembrane proteins that mediate cell-cell adhesion at adherens junctions. A complex chain of cis- and trans- interactions between... (Review)
Review
Classical cadherins are a family of transmembrane proteins that mediate cell-cell adhesion at adherens junctions. A complex chain of cis- and trans- interactions between cadherin ectodomains establishes a cadherin adhesive cluster. A principal adhesive interaction in such clusters is an exchange of β strands between the first extracellular cadherin domains (EC1). The structure of cadherin adhesive clusters can be modified by other adherens junction proteins including additional transmembrane proteins, nectins and various intracellular proteins that directly or indirectly interact with the intracellular cadherin region. These interactions determine the dynamics and stability of cadherin adhesive structures.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Humans; Models, Molecular; Protein Multimerization
PubMed: 22674069
DOI: 10.1007/978-94-007-4186-7_5 -
International Review of Cell and... 2012Adherens junctions are essential for the development and physiology of epithelial tissues. The Drosophila embryo is an excellent model for understanding adherens... (Review)
Review
Adherens junctions are essential for the development and physiology of epithelial tissues. The Drosophila embryo is an excellent model for understanding adherens junction assembly, maintenance, and regulation during tissue development. Here, I review our current state of knowledge in this model system. The review begins by outlining the structure of the cadherin-catenin complex in Drosophila including core (DE-cadherin, Armadillo, α-catenin, and p120-catenin) and peripheral proteins. Then, it summarizes adherens junction assembly at cellularization and maturation at gastrulation. Finally, the regulation of adherens junctions during tissue morphogenesis is discussed. This discussion compares major morphogenetic events in the embryo (invagination of the ventral furrow, convergent extension of the germband, flattening of the amnioserosa, maintenance of tissue borders, epithelial branching, lumen formation, cell delamination, cell division, apoptosis, and dorsal closure) and common mechanisms involved (myosin activity, endocytosis, and mesenchymal-to-epithelial transitions).
Topics: Adherens Junctions; Animals; Armadillo Domain Proteins; Cadherins; Drosophila; Drosophila Proteins; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Models, Biological; Morphogenesis; Protein Binding; Protein Multimerization; alpha Catenin
PubMed: 22251558
DOI: 10.1016/B978-0-12-394304-0.00007-5 -
Cellular and Molecular Life Sciences :... Sep 2016E-Cadherin-based Adherens Junctions (AJs) are a defining feature of all epithelial sheets. Through the homophilic association of E-Cadherin molecules expressed on... (Review)
Review
E-Cadherin-based Adherens Junctions (AJs) are a defining feature of all epithelial sheets. Through the homophilic association of E-Cadherin molecules expressed on neighboring cells, they ensure intercellular adhesion amongst epithelial cells, and regulate many key aspects of epithelial biology. While their adhesive role requires these structures to remain stable, AJs are also extremely plastic. This plasticity allows for the adaptation of the cell to its changing environment: changes in neighbors after cell division, cell death, or cell movement, and changes in cell shape during differentiation. In this review we focus on the recent advances highlighting the critical role of the apico-basal polarity machinery, and in particular of the Par3/Bazooka scaffold, in the regulation and remodeling of AJs. We propose that by regulating key phosphorylation events on the core E-Cadherin complex components, Par3 and epithelial polarity promote meta-stable protein complexes governing the correct formation, localization, and functioning of AJ.
Topics: Adherens Junctions; Animals; Cadherins; Catenins; Cell Polarity; Epithelial Cells; Membrane Proteins; Phosphoric Monoester Hydrolases; src-Family Kinases
PubMed: 27151512
DOI: 10.1007/s00018-016-2260-8 -
Developmental Cell Oct 2018During epithelial tissue development, repair, and homeostasis, adherens junctions (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell and... (Review)
Review
During epithelial tissue development, repair, and homeostasis, adherens junctions (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell and tissue dynamics. Mechanical forces play critical roles in AJs' composition and dynamics. Recent findings highlight that beyond a well-established role in reinforcing cell-cell adhesion, AJ mechanosensitivity promotes junctional remodeling and polarization, thereby regulating critical processes such as cell intercalation, division, and collective migration. Here, we provide an integrated view of mechanosensing mechanisms that regulate cell-cell contact composition, geometry, and integrity under tension and highlight pivotal roles for mechanosensitive AJ remodeling in preserving epithelial integrity and sustaining tissue dynamics.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Epithelial Cells; Epithelium; Humans; Mechanotransduction, Cellular; Morphogenesis
PubMed: 30300588
DOI: 10.1016/j.devcel.2018.09.014 -
Cold Spring Harbor Perspectives in... Dec 2009The adherens junction (AJ) is an element of the cell-cell junction in which cadherin receptors bridge the neighboring plasma membranes via their homophilic interactions.... (Review)
Review
The adherens junction (AJ) is an element of the cell-cell junction in which cadherin receptors bridge the neighboring plasma membranes via their homophilic interactions. Cadherins associate with cytoplasmic proteins, called catenins, which in turn bind to cytoskeletal components, such as actin filaments and microtubules. These molecular complexes further interact with other proteins, including signaling molecules, rendering the AJs into highly dynamic and regulatable structures. The AJs of such nature contribute to the physical linking of cells, as well as to the regulation of cell-cell contacts, which is essential for morphogenesis and remodeling of tissues and organs. Thus, elucidating the molecular architecture of the AJs and their regulatory mechanisms are crucial for understanding how the multicellular system is organized.
Topics: Adherens Junctions; Animals; Cadherins; Catenins; Cell Polarity; Cytoskeleton
PubMed: 20457565
DOI: 10.1101/cshperspect.a002899 -
Sub-cellular Biochemistry 2012The cadherin/catenin complex organizes to form a structural Velcro that joins the cytoskeletal networks of adjacent cells. Functional loss of this complex arrests the... (Review)
Review
The cadherin/catenin complex organizes to form a structural Velcro that joins the cytoskeletal networks of adjacent cells. Functional loss of this complex arrests the development of normal tissue organization, and years of research have gone into teasing out how the physical structure of adhesions conveys information to the cell interior. Evidence that most cadherin-binding partners also localize to the nucleus to regulate transcription supports the view that cadherins serve as simple stoichiometric inhibitors of nuclear signals. However, it is also clear that cadherin-based adhesion initiates a variety of molecular events that can ultimately impact nuclear signaling. This chapter discusses these two modes of cadherin signaling in the context of tissue growth and differentiation.
Topics: Adherens Junctions; Animals; Humans; Signal Transduction
PubMed: 22674072
DOI: 10.1007/978-94-007-4186-7_8 -
Bioscience Reports Apr 2018In healthy individuals, any rise in blood glucose levels is rapidly countered by the release of insulin from the β-cells of the pancreas which in turn promotes the... (Review)
Review
In healthy individuals, any rise in blood glucose levels is rapidly countered by the release of insulin from the β-cells of the pancreas which in turn promotes the uptake and storage of the glucose in peripheral tissues. The β-cells possess exquisite mechanisms regulating the secretion of insulin to ensure that the correct amount of insulin is released. These mechanisms involve tight control of the movement of insulin containing secretory vesicles within the β-cells, initially preventing most vesicles being able to move to the plasma membrane. Elevated glucose levels trigger an influx of Ca that allows fusion of the small number of insulin containing vesicles that are pre-docked at the plasma membrane but glucose also stimulates processes that allow other insulin containing vesicles located further in the cell to move to and fuse with the plasma membrane. The mechanisms controlling these processes are complex and not fully understood but it is clear that the interaction of the β-cells with other β-cells in the islets is very important for their ability to develop the appropriate machinery for proper regulation of insulin secretion. Emerging evidence indicates one factor that is key for this is the formation of homotypic cadherin mediated adherens junctions between β-cells. Here, we review the evidence for this and discuss the mechanisms by which these adherens junctions might regulate insulin vesicle trafficking as well as the implications this has for understanding the dysregulation of insulin secretion seen in pathogenic states.
Topics: Adherens Junctions; Animals; Calcium Signaling; Glucose; Humans; Insulin; Insulin-Secreting Cells
PubMed: 29459424
DOI: 10.1042/BSR20170989 -
Sub-cellular Biochemistry 2012Adherens junctions are important mediators of intercellular adhesion, but they are not static structures. They are regularly formed, broken, and rearranged in a variety... (Review)
Review
Adherens junctions are important mediators of intercellular adhesion, but they are not static structures. They are regularly formed, broken, and rearranged in a variety of situations, requiring changes in the amount of cadherins, the main adhesion molecule in adherens junctions, present at the cell surface. Thus, endocytosis, degradation, and recycling of cadherins are crucial for dynamic regulation of adherens junctions and control of intercellular adhesion. In this chapter, we review the involvement of cadherin endocytosis in development and disease. We discuss the various endocytic pathways available to cadherins, the adaptors involved, and the sorting of internalized cadherin for recycling or lysosomal degradation. In addition, we review the regulatory pathways controlling cadherin endocytosis and degradation, including regulation of cadherin endocytosis by catenins, cadherin ubiquitination, and growth factor receptor signaling pathways. Lastly, we discuss the proteolytic cleavage of cadherins at the plasma membrane.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Endocytosis; Humans; Protein Transport; Proteolysis; Signal Transduction
PubMed: 22674073
DOI: 10.1007/978-94-007-4186-7_9 -
Journal of Andrology 2003
Review
Topics: Adherens Junctions; Animals; Humans; Male; Signal Transduction; Spermatogenesis; Testis
PubMed: 12514071
DOI: No ID Found