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Cell and Tissue Research Jun 2015The epithelial monolayer of the intestine is a selective barrier permitting nutrient and electrolyte absorption yet acting to protect the underlying tissue compartments... (Review)
Review
The epithelial monolayer of the intestine is a selective barrier permitting nutrient and electrolyte absorption yet acting to protect the underlying tissue compartments and cellular components from attack and infiltration by antigens, bacteria and bacterial products present in the lumen. Disruption of this barrier has been associated with inflammatory bowel disease (IBD). The adherens junction (AJ), together with tight junctions (TJ) and desmosomes, form an apical junction complex that controls epithelial cell-to-cell adherence and barrier function as well as regulation of the actin cytoskeleton, intracellular signalling pathways and transcriptional regulation. Numerous studies and reviews highlight the responses of TJs to physiological and pathological stimuli. By comparison, the response of AJ proteins, and the subsequent consequences for barrier function, when exposed to the IBD inflammatory milieu, is less well studied. In this review, we will highlight the roles and responses of the AJ proteins in IBD and provide suggestions for future studies. We will also consider recently proposed therapeutic strategies to preserve or restore epithelial barrier functions to prevent and treat IBD.
Topics: Adherens Junctions; Animals; Cadherins; Epithelium; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; beta Catenin
PubMed: 25238996
DOI: 10.1007/s00441-014-1994-6 -
Cell Adhesion & Migration 2015This review addresses our current understanding of the regulatory mechanism by which N-cadherin, a classical cadherin, affects neural progenitor cells (NPCs) during... (Review)
Review
This review addresses our current understanding of the regulatory mechanism by which N-cadherin, a classical cadherin, affects neural progenitor cells (NPCs) during development. N-cadherin is responsible for the integrity of adherens junctions (AJs), which develop in the sub-apical region of NPCs in the neural tube and brain cortex. The apical domain, which contains the sub-apical region, is involved in the switching from symmetric proliferative division to asymmetric neurogenic division of NPCs. In addition, N-cadherin-based AJ is deeply involved in the apico-basal polarity of NPCs and the regulation of Wnt-β-catenin, hedgehog (Hh), and Notch signaling. In this review, we discuss the roles of N-cadherin in the maintenance, proliferation, and differentiation of NPCs through components of AJ, β-catenin and αE-catenin.
Topics: Adherens Junctions; Animals; Cadherins; Cell Differentiation; Cell Polarity; Cell Proliferation; Hedgehog Proteins; Humans; Mice; Neural Stem Cells; Neural Tube; Signal Transduction; beta Catenin
PubMed: 25869655
DOI: 10.1080/19336918.2015.1005466 -
The Journal of Cell Biology Dec 2021Embryogenesis requires cells to change shape and move without disrupting epithelial integrity. This requires robust, responsive linkage between adherens junctions and...
Embryogenesis requires cells to change shape and move without disrupting epithelial integrity. This requires robust, responsive linkage between adherens junctions and the actomyosin cytoskeleton. Using Drosophila morphogenesis, we define molecular mechanisms mediating junction-cytoskeletal linkage and explore the role of mechanosensing. We focus on the junction-cytoskeletal linker Canoe, a multidomain protein. We engineered the canoe locus to define how its domains mediate its mechanism of action. To our surprise, the PDZ and FAB domains, which we thought connected junctions and F-actin, are not required for viability or mechanosensitive recruitment to junctions under tension. The FAB domain stabilizes junctions experiencing elevated force, but in its absence, most cells recover, suggesting redundant interactions. In contrast, the Rap1-binding RA domains are critical for all Cno functions and enrichment at junctions under tension. This supports a model in which junctional robustness derives from a large protein network assembled via multivalent interactions, with proteins at network nodes and some node connections more critical than others.
Topics: Adherens Junctions; Alleles; Animals; Cell Survival; Cytoskeleton; Drosophila Proteins; Drosophila melanogaster; Epithelium; Loss of Function Mutation; Morphogenesis; Protein Domains
PubMed: 34762121
DOI: 10.1083/jcb.202104087 -
Stroke Jun 2002This review deals with the role of calcium in endothelial cell junctions of the blood-brain barrier (BBB). Calcium is critical for adherens junction function, but it... (Review)
Review
BACKGROUND
This review deals with the role of calcium in endothelial cell junctions of the blood-brain barrier (BBB). Calcium is critical for adherens junction function, but it appears that calcium is also important in regulating tight junction function necessary for the barrier characteristics of cerebral microvessels.
SUMMARY OF REVIEW
The BBB is critical for brain homeostasis and is located at the cerebral microvessel endothelial cells. These endothelial cells maintain their barrier characteristics via cell-cell contacts made up of adherens and tight junctions. Adherens junctions are calcium dependent; recent evidence suggests that calcium also affects tight junctions. After stroke, there is a disruption of the BBB. Interfering with calcium flux under hypoxic conditions can prevent BBB breakdown. Calcium may alter BBB junction integrity by a number of different signal transduction cascades, as well as via direct interaction of calcium ions with junction proteins. It remains to be determined whether clinical use of calcium channel antagonists is a viable means to reduce BBB disruption after stroke.
CONCLUSIONS
With the widespread use of calcium channel blockers as clinical treatments for hypertension, which is a risk factor for stroke, the exact role of calcium in modulating BBB integrity needs to be elucidated.
Topics: Adherens Junctions; Animals; Blood-Brain Barrier; Calcium; Endothelium, Vascular; Humans; Signal Transduction; Stroke; Tight Junctions
PubMed: 12053015
DOI: 10.1161/01.str.0000016405.06729.83 -
Nature Cell Biology Jul 2014Collective cell migration is essential for both physiological and pathological processes. Adherens junctions (AJs) maintain the integrity of the migrating cell group and...
Collective cell migration is essential for both physiological and pathological processes. Adherens junctions (AJs) maintain the integrity of the migrating cell group and promote cell coordination while allowing cellular rearrangements. Here, we show that AJs undergo a continuous treadmilling along the lateral sides of adjacent leading cells. The treadmilling is driven by an actin-dependent rearward movement of AJs and is supported by the polarized recycling of N-cadherin. N-cadherin is mainly internalized at the cell rear and then recycled to the leading edge where it accumulates before being incorporated into forming AJs at the front of lateral cell-cell contacts. The polarized dynamics of AJs is controlled by a front-to-rear gradient of p120-catenin phosphorylation, which regulates polarized trafficking of N-cadherin. Perturbation of the GSK3-dependent phosphorylation of p120-catenin impacts on the stability of AJs, and the polarity and speed of leading cells during collective migration.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Cell Movement; Cells, Cultured; Glycogen Synthase Kinase 3; Mice; NIH 3T3 Cells; Optical Imaging; Phosphorylation; Rats
PubMed: 24929360
DOI: 10.1038/ncb2985 -
Current Biology : CB May 2022Tissue morphogenesis arises from the culmination of changes in cell-cell junction length. Mechanochemical signaling in the form of RhoA underlies these ratcheted...
Tissue morphogenesis arises from the culmination of changes in cell-cell junction length. Mechanochemical signaling in the form of RhoA underlies these ratcheted contractions, which occur asymmetrically. The underlying mechanisms of asymmetry remain unknown. We use optogenetically controlled RhoA in model epithelia together with biophysical modeling to uncover the mechanism lending to asymmetric vertex motion. Using optogenetic and pharmacological approaches, we find that both local and global RhoA activation can drive asymmetric junction contraction in the absence of tissue-scale patterning. We find that standard vertex models with homogeneous junction properties are insufficient to recapitulate the observed junction dynamics. Furthermore, these experiments reveal a local coupling of RhoA activation with E-cadherin accumulation. This motivates a coupling of RhoA-mediated increases in tension and E-cadherin-mediated adhesion strengthening. We then demonstrate that incorporating this force-sensitive adhesion strengthening into a continuum model is successful in capturing the observed junction dynamics. Thus, we find that a force-dependent intercellular "clutch" at tricellular vertices stabilizes vertex motion under increasing tension and is sufficient to generate asymmetries in junction contraction.
Topics: Adherens Junctions; Cadherins; Cell Adhesion; Epithelial Cells; Epithelium; Morphogenesis
PubMed: 35381185
DOI: 10.1016/j.cub.2022.03.024 -
Acta Histochemica Mar 2016During early pregnancy in the rat, the luminal uterine epithelial cells (UECs) must transform to a receptive state to permit blastocyst attachment and implantation. The... (Comparative Study)
Comparative Study
During early pregnancy in the rat, the luminal uterine epithelial cells (UECs) must transform to a receptive state to permit blastocyst attachment and implantation. The implantation process involves penetration of the epithelial barrier, so it is expected that the transformation of UECs includes alterations in the lateral junctional complex. Previous studies have demonstrated a deepening of the tight junction (zonula occludens) and a reduction in the number of desmosomes (macula adherens) in UECs at the time of implantation. However, the adherens junction (zonula adherens), which is primarily responsible for cell-cell adhesion, has been little studied during early pregnancy. This study investigated the adherens junction in rat UECs during the early stages of normal pregnancy and ovarian hyperstimulated (OH) pregnancy using transmission electron microscopy. The adherens junction is present in UECs at the time of fertilisation, but is lost at the time of blastocyst implantation during normal pregnancy. Interestingly, at the time of implantation after OH, adherens junctions are retained and may impede blastocyst penetration of the epithelium. The adherens junction anchors the actin-based terminal web, which is known to be disrupted in UECs during early pregnancy. However, artificial disruption of the terminal web, using cytochalasin D, did not cause removal of the adherens junction in UECs. This study revealed that adherens junction disassembly occurs during early pregnancy, but that this process does not occur during OH pregnancy. Such disassembly does not appear to depend on the disruption of the terminal web.
Topics: Adherens Junctions; Animals; Cytoskeleton; Embryo Implantation; Epithelial Cells; Female; Ovulation Induction; Pregnancy; Rats, Wistar; Uterus
PubMed: 26738975
DOI: 10.1016/j.acthis.2015.12.004 -
The Journal of Cell Biology Jun 2011Adhesion between cells is essential to the evolution of multicellularity. Indeed, morphogenesis in animals requires firm but flexible intercellular adhesions that are... (Review)
Review
Adhesion between cells is essential to the evolution of multicellularity. Indeed, morphogenesis in animals requires firm but flexible intercellular adhesions that are mediated by subcellular structures like the adherens junction (AJ). A key component of AJs is classical cadherins, a group of transmembrane proteins that maintain dynamic cell-cell associations in many animal species. An evolutionary reconstruction of cadherin structure and function provides a comprehensive framework with which to appreciate the diversity of morphogenetic mechanisms in animals.
Topics: Adherens Junctions; Animals; Cadherins; Cell Adhesion; Drosophila; Drosophila Proteins; Embryo, Nonmammalian; Evolution, Molecular; Mice; Protein Structure, Tertiary; Structure-Activity Relationship
PubMed: 21708975
DOI: 10.1083/jcb.201008173 -
Trends in Biochemical Sciences Feb 2016The actin cytoskeleton and adhesion junctions are physically and functionally coupled at the cell-cell interface between epithelial cells. The actin regulatory complex... (Review)
Review
The actin cytoskeleton and adhesion junctions are physically and functionally coupled at the cell-cell interface between epithelial cells. The actin regulatory complex Arp2/3 has an established role in the turnover of junctional actin; however, the role of formins, the largest group of actin regulators, is less clear. Formins dynamically shape the actin cytoskeleton and have various functions within cells. In this review we describe recent progress on how formins regulate actin dynamics at cell-cell contacts and highlight formin functions during polarized protein traffic necessary for epithelialization.
Topics: Actin Cytoskeleton; Adherens Junctions; Animals; Epithelium; Humans
PubMed: 26732401
DOI: 10.1016/j.tibs.2015.12.002 -
FASEB Journal : Official Publication of... Mar 2023Adherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key...
Adherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key step in tumor metastasis. AJ remodeling is crucial for cancer progression, and it plays a key role in tumor cell survival, growth, and dissemination. Few studies have examined AJ remodeling in cancer cells consequently, it remains poorly understood and unleveraged in the treatment of metastatic carcinomas. Fascin1 is an actin-bundling protein that is absent from the normal epithelium but its expression in colon cancer is linked to metastasis and increased mortality. Here, we provide the molecular mechanism of AJ remodeling in colon cancer cells and identify for the first time, fascin1's function in AJ remodeling. We show that in colon cancer cells fascin1 remodels junctional actin and actomyosin contractility which makes AJs less stable but more dynamic. By remodeling AJs fascin1 drives mechanoactivation of WNT/β-catenin signaling and generates "collective plasticity" which influences the behavior of cells during cell migration. The impact of mechanical inputs on WNT/β-catenin activation in cancer cells remains poorly understood. Our findings highlight the role of AJ remodeling and mechanosensitive WNT/β-catenin signaling in the growth and dissemination of colorectal carcinomas.
Topics: Humans; Adherens Junctions; Actins; beta Catenin; Microfilament Proteins; Colonic Neoplasms; Cadherins
PubMed: 36786724
DOI: 10.1096/fj.202201454R