A short guide to the tight junction

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(9)

Published: May 1, 2024

ABSTRACT Tight junctions (TJs) are specialized regions of contact between cells epithelial and endothelial tissues that form selective semipermeable paracellular barriers establish maintain body compartments with different fluid compositions. As such, the formation TJs represents a critical step in metazoan evolution, allowing multicompartmental organisms true, barrier-forming epithelia endothelia. In six decades have passed since first observations by transmission electron microscopy, much progress has been made understanding structure, function, molecular composition regulation TJs. The goal this Perspective is to highlight key concepts emerged through research future challenges lie ahead for field.

Language: Английский

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α-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak

Biology Open, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 8, 2025

ABSTRACT Epithelial cell cohesion and barrier function critically depend on α-catenin, an actin-binding protein essential constituent of cadherin-catenin-based adherens junctions. α-catenin undergoes actomyosin force-dependent unfolding both middle domains to strongly engage actin filaments its various effectors; this mechanosensitivity is critical for junction function. We previously showed that highly phosphorylated in unstructured region links the mechanosensitive (known as P-linker region), but cellular processes promote phosphorylation have remained elusive. Here, we leverage a published phospho-proteomic data set show maximally during mitosis. By reconstituting CRISPR knockout MDCK cells with wild-type, phospho-mutant phospho-mimic forms full restrains mitotic rounding apical direction, strengthening interactions between dividing non-dividing neighbors limit epithelial leak. As major scaffold components junctions, tight junctions desmosomes are also differentially mitosis, reason division may be tractable system understand how complexes coordinately regulated sustain under tension-generating morphogenetic processes.

Language: Английский

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Damage control of epithelial barrier function in dynamic environments

European Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 103(2), P. 151410 - 151410

Published: April 3, 2024

Epithelial tissues cover the surfaces and lumens of internal organs multicellular animals crucially contribute to environment homeostasis by delineating distinct compartments within body. This vital role is known as epithelial barrier function. cells are arranged like cobblestones intricately bind together form an sheet that upholds this Central restriction solute fluid diffusion through intercellular spaces occluding junctions, tight junctions in vertebrates septate invertebrates. As part tissues, undergo constant renewal, with older being replaced new ones. Simultaneously, tissue undergoes relative rearrangement, elongating, shifting directionally a whole. The movement or shape changes necessitate significant deformation reconnection junctions. Recent advancements have shed light on intricate mechanisms which sustain their function dynamic environments. review aims introduce these noteworthy findings discuss some questions remain unanswered.

Language: Английский

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Interplay of damage and repair in the control of epithelial tissue integrity in response to cyclic loading

Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 94, P. 102511 - 102511

Published: April 14, 2025

Epithelial tissues are continuously exposed to cyclic stretch in vivo. Physiological stretching has been found regulate soft tissue function at the molecular, cellular, and scales, allowing preserve their homeostasis adapt challenges. In contrast, dysregulated or pathological can induce damage fragilisation. Many mechanisms have described for repair of epithelial across a range timescales. this review, we present timescales (i) physiological loading regimes, (ii) strain-regulated remodeling accumulation, (iii) tissues. We discuss how response biological differs from synthetic materials, that be partially fully reversed by acting on shorter than loading. highlight critical understanding interplay between experience loading, opening up new avenues exploring homeostasis.

Language: Английский

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Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions

Biology Open, Journal Year: 2025, Volume and Issue: 14(2)

Published: Jan. 30, 2025

The network of proteins at the interface between cell-cell adherens junctions and actomyosin cytoskeleton provides robust yet dynamic connections that facilitate cell shape change motility. While this was initially thought to be a simple linear connection via classic cadherins their associated catenins, we now have come appreciate many more are involved, providing robustness mechanosensitivity. Defining full set in remains key objective our field. Proximity proteomics means define these networks. Mammalian Afadin its Drosophila homolog Canoe parts protein network, facilitating diverse changes during gastrulation other events embryonic morphogenesis. Here report results several proximity screens, defining neighborhood both N- C-termini mammalian premier epithelial model, MDCK cells. We compare with previous screens done types, efforts junctional proteins. These reveal value multiple neighbors offer interesting insights into overlap composition different junctions.

Language: Английский

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Afadin-deficient retinas exhibit severe neuronal lamination defects but preserve visual functions

Published: Feb. 14, 2025

Neural lamination is a common feature of the central nervous system (CNS), with several subcellular structures, such as adherens junctions (AJs), playing role in this process. The retina also heavily laminated, but it remains unclear how laminar formation impacts retinal cell morphology, synapse integrity, and overall function. In study, we demonstrate that loss afadin, key component AJs, leads to significant pathological changes. These include disruption outer notable decrease well mislocalization photoreceptors, their segments, photoreceptor synapses. Interestingly, despite these severe impairments, recorded small local field potentials, including a- b-waves. We classified ganglion cells into ON, ON-OFF, OFF types based on firing patterns response light stimuli. Additionally, successfully characterized receptive fields certain cells. Overall, findings provide first evidence circuit function can be partially preserved even when there are disruptions Our results indicate retinas severely altered morphology still retain some capacity process

Language: Английский

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Afadin-deficient retinas exhibit severe neuronal lamination defects but preserve visual functions

Published: Feb. 14, 2025

Neural lamination is a common feature of the central nervous system (CNS), with several subcellular structures, such as adherens junctions (AJs), playing role in this process. The retina also heavily laminated, but it remains unclear how laminar formation impacts retinal cell morphology, synapse integrity, and overall function. In study, we demonstrate that loss afadin, key component AJs, leads to significant pathological changes. These include disruption outer notable decrease well mislocalization photoreceptors, their segments, photoreceptor synapses. Interestingly, despite these severe impairments, recorded small local field potentials, including a- b-waves. We classified ganglion cells into ON, ON-OFF, OFF types based on firing patterns response light stimuli. Additionally, successfully characterized receptive fields certain cells. Overall, findings provide first evidence circuit function can be partially preserved even when there are disruptions Our results indicate retinas severely altered morphology still retain some capacity process

Language: Английский

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Multivalent afadin interaction promotes IDR-mediated condensate formation and junctional separation of epithelial cells

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115335 - 115335

Published: Feb. 1, 2025

In epithelial cells, cell-cell adhesion is mediated by the apical junctional complex (AJC), which consists of tight junctions (TJs) and adherens (AJs) aligned from to basal axis. However, mechanism AJC formation on side separation these within AJCs are poorly understood. We find that multivalent interactions afadin with molecules cytoskeleton lead condensate in an intrinsically disordered region (IDR)-dependent manner, promotes efficient accumulation linear AJ during initial junction formation. Furthermore, we observe ZO-1 induce different formations cell differentially distributed each other. These properties explain how it strictly localizes AJs cells involved regulating segregation TJs AJC.

Language: Английский

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Afadin loss induces breast cancer metastasis through destabilisation of E‐cadherin to F‐actin linkage

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Afadin is a multimodal scaffolding protein with essential functions in cell–cell adhesion. Although its loss of expression has been linked to breast cancer invasion and metastasis, the underlying mechanisms driving tumour progression upon mutational ( AFDN ) cancers remains unclear. In current study we identified somatic frameshift mutation p .Lys630fs) an invasive sample that coincides expression. Functional studies E‐cadherin‐expressing cells show leads immature aberrant adherens junction (AJ) formation. The lack AJ maturation results noncohesive cellular phenotype accompanied by Actomyosin‐dependent anoikis resistance, which are classical hallmarks single‐cell invasion. Reconstitution experiments using truncates proper F‐actin organisation epithelial adhesion critically depend on Coiled‐Coil domain but not designated C‐terminal binding domain. Mouse xenograft based cell lines primary patient‐derived organoids demonstrate induces lobular‐type phenotypes overt dissemination lungs peritoneum. short, metastasis suppressor for through stabilisation mechanical E‐cadherin outside‐in link. © 2025 Author(s). Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Language: Английский

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Co-Exposure to Polystyrene Microplastics and Bisphenol A Contributes to the Formation of Liver Fibrosis in Mice through Inhibition of the BMAL1/E-Cad Signaling Pathway

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

The food safety risks posed by exposure to polystyrene microplastics (PS-MPs) and bisphenol A (BPA) have become an issue worldwide. However, the toxic effects of PS-MPs BPA coexposure on mammalian liver remain elusive. In this study, we found that synergistic AML12 cells mouse liver. Histopathological staining revealed excessive accumulation extracellular matrix in Co-exposure downregulated Bmal1 E-cad both vitro vivo. Additionally, Bmal1–/– liver-specific mice exhibited significantly reduced levels, with no significant reduction under coexposure. Notably, overexpression BMAL1 CLOCK enhanced luciferase activity driven gene intron region (containing E-box cis-element). These results demonstrated contributed development fibrosis inhibiting BMAL1/E-cad signaling pathway.

Language: Английский

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