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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The zonula adherens matura redefines the apical junction of intestinal epithelia

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(9)

Published: Feb. 20, 2024

Cell–cell apical junctions of epithelia consist multiprotein complexes that organize as belts regulating cell–cell adhesion, permeability, and mechanical tension: the tight junction ( zonula occludens ), adherens ZA macula . The prevailing dogma is at , E-cadherin catenins are lined with F-actin bundles support transmit tension between cells. Using super-resolution microscopy on human intestinal biopsies Caco-2 cells, we show two distinct basal mature. most populated nectins/afadin F-actin; second E-cad/catenins. We name this dual-belt architecture matura find contraction apparatus organization rely afadin expression. Our study provides a revised description epithelial identifies module mechanics epithelia.

Language: Английский

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Biophysics of claudin proteins in tight junction architecture: three decades of progress

Biophysical Journal, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

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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Wall of Resilience: How the Intestinal Epithelium Prevents Inflammatory Onslaught in the Gut

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: unknown, P. 101423 - 101423

Published: Oct. 1, 2024

The intestinal epithelium forms the boundary between immune system in lamina propria and outside world, lumen, which contains a diverse array of microbial environmental antigens. Composed specialized cells, this epithelial monolayer has an exceptional turnover rate. Differentiated cells are released into lumen within few days, at villus tip, process that requires strict regulation. Dysfunction barrier increases permeability paves way for luminal antigens to pass serosa. Stem bottom Lieberkühn crypts provide constant supply mature cells. exhibit mechanisms enable communication with surrounding fortification against microorganisms, orchestration nutrient absorption hormonal balance. Furthermore, tight junctions regulate paracellular properties, their disruption can lead impairment barrier, allowing inflammation develop or further progress. Intestinal platform through they maintain homeostasis spectrum entities including neuronal connective tissue This be disrupted disease, such as inflammatory bowel disease. Patients suffering from disease show impaired gut dysregulated cellular communication, aberrant proliferation demise review summarizes individual molecular pivotal upholding integrity shows how these diseases,

Language: Английский

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Checkerboard Cellular Pattern in Auditory Epithelia: Implications for Auditory Function and Sensory Pathology

Hearing Research, Journal Year: 2025, Volume and Issue: unknown, P. 109220 - 109220

Published: Feb. 1, 2025

Sensory epithelia are composed of specialized cells arranged in specific patterns essential for function. The auditory epithelium the organ Corti features a highly conserved checkerboard pattern mechanosensory hair and supporting cells, preventing direct cell contact preserving epithelial integrity. In mice, disruption this results deafness due to apoptosis caused by abnormal adherens tight junction formation structural fragility. This is evolutionarily across species, highlighting its functional significance. Direct contact, which normally does not occur, leads adhesion molecule accumulation, altered ion permeability, subsequent death. likely evolved optimize hair-supporting interactions while maintaining stability. review explores physiological significance cellular arrangement function consequences disruption, hearing loss. Understanding mechanisms governing may provide insights into disorders potential therapeutic approaches.

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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ARHGAP12 suppresses F-actin assembly to control epithelial tight junction mechanics and paracellular leak pathway permeability

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115511 - 115511

Published: April 1, 2025

Tight junctions (TJs) control the paracellular transport of ions, solutes, and macromolecules across epithelial barriers. There is evidence that claudin-based ion (the pore pathway) leak are controlled independently. However, how pathway flux regulated unclear. Here, we have identified Cdc42/Rac GTPase-activating protein ARHGAP12 as a specific activator pathway. recruited to TJs via an interaction between its Src homology (SH3) domain TJ ZO-2 suppress N-WASP-mediated F-actin assembly. This dampens junctional tension promotes without affecting flux. Mechanistically, demonstrate tandem WW interacts directly with PPxR motifs in proline-rich N-WASP thereby attenuates SH3-domain-mediated oligomerization Arp2/3-driven Collectively, our data indicate branched networks regulate fine-tune

Language: Английский

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Cell–cell junctions in focus – imaging junctional architectures and dynamics at high resolution

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(20)

Published: Oct. 15, 2024

ABSTRACT Studies utilizing electron microscopy and live fluorescence have significantly enhanced our understanding of the molecular mechanisms that regulate junctional dynamics during homeostasis, development disease. To fully grasp enormous complexity cell–cell adhesions, it is crucial to study nanoscale architectures tight junctions, adherens junctions desmosomes. It important integrate these with membrane morphology cellular topography in which are embedded. In this Review, we explore new insights from studies using super-resolution volume into organization complexes as well roles junction-associated cytoskeleton, neighboring organelles plasma membrane. Furthermore, provide an overview junction- cytoskeletal-related biosensors optogenetic probes contributed advances discuss how tools enhance across environments.

Language: Английский

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ARHGAP12 suppresses F-actin assembly to control epithelial tight junction mechanics and paracellular leak pathway permeability

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 26, 2024

Abstract Tight junctions (TJ) separate body compartments and control the paracellular transport of ions, solutes, macromolecules across epithelial barriers. There is evidence that claudin-based ion (the pore pathway) leak are independently regulated processes. However, how pathway permeability controlled not well understood. Here we have identified Cdc42/Rac GTPase activating protein ARHGAP12 as a novel specific regulator pathway. recruited to TJ via an interaction between its SH3 domain ZO-2. Using combination biochemical biophysical approaches, in vitro actin polymerisation assays, assays MDCK-II cells, show suppresses N-WASP-mediated F-actin assembly at dampen junctional tension. This promotes without affecting flux. Mechanistically, demonstrate tandem WW interacts directly multivalent manner with array PPxR motifs proline-rich N-WASP. sufficient suppress domain-mediated N-WASP oligomerisation Arp2/3-driven vitro. Collectively our data critical role for suppressing tension promote flux small TJ.

Language: Английский

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