ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism sensing paracellular diffusion barrier alteration inDrosophilaepithelial cells DOI Open Access
Thomas Esmangart de Bournonville, Mariusz K. Jaglarz,

Emeline Durel

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 24, 2023

Summary Barrier functions of proliferative epithelia are constantly challenged by mechanical and chemical constraints. How respond to cope with disturbances the paracellular diffusion barrier allow tissue integrity maintenance has been poorly characterized. Cellular junctions play an important role in this process intracellular traffic contribute their homeostasis. Here, we reveal that, Drosophila pupal notum, alteration bi- or tricellular septate (SJs) triggers a mechanism two prominent outcomes. On one hand, there is increase levels E-cadherin, F- Actin non-muscle myosin II plane adherens junctions. other β-integrin/Vinculin-positive cell contacts reinforced along lateral basal membranes. We report that weakening SJ integrity, caused depletion components, reduces ESCRT-III/Vps32/Shrub-dependent degradation promotes instead Retromer-dependent recycling components. The consequence reduction Shrub-dependent extends transmembrane protein cargoes. Consequently, trigger increased β- integrin, Crumbs effectors β-Heavy Spectrin Karst. propose which epithelial cells, upon sensing alterations barrier, target Shrub adjust degradation/recycling balance thereby compensate for defects while maintaining integrity.

Язык: Английский

ZnUMBA – a live imaging method to detect local barrier breaches DOI Creative Commons
Tomohito Higashi, Rachel E. Stephenson, Cornelia Schwayer

и другие.

Journal of Cell Science, Год журнала: 2023, Номер 136(15)

Опубликована: Июль 18, 2023

Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage the monolayer. Although these methods measure changes in global function, they lack sensitivity needed to detect local transient breaches, do not reveal location of leaks. Therefore, we previously developed method that named zinc-based ultrasensitive microscopic assay (ZnUMBA), overcomes limitations, allowing for detection tight junction leaks with high spatiotemporal resolution. Here, present expanded applications ZnUMBA. ZnUMBA can be used Xenopus embryos dynamics restoration actin accumulation following laser injury. also effectively utilized developing zebrafish as well cultured monolayers Madin-Darby canine kidney (MDCK) II epithelial cells. powerful flexible that, minimal optimization, applied multiple systems dynamic precision.

Язык: Английский

Процитировано

8
Claudin-4 polymerizes after a small extracellular claudin-3-like substitution DOI Creative Commons
Rozemarijn E. van der Veen, Jörg Piontek,

Marie Bieck

и другие.

Journal of Biological Chemistry, Год журнала: 2024, Номер 300(10), С. 107693 - 107693

Опубликована: Авг. 17, 2024

Язык: Английский

Процитировано

1
Molecular basis of proteolytic cleavage regulation by the extracellular matrix receptor dystroglycan DOI
Michael J. Anderson, Amanda N Hayward, Adam T. Smiley

и другие.

Structure, Год журнала: 2024, Номер 32(11), С. 1984 - 1996.e5

Опубликована: Сен. 20, 2024

Язык: Английский

Процитировано

1
Rho-ROCK liberates sequestered claudin for rapid de novo tight junction formation DOI Open Access
Yuma Cho,

Akari Taniguchi,

Akiharu Kubo

и другие.

Опубликована: Ноя. 22, 2024

The epithelial cell sheet maintains its integrity as a barrier while undergoing turnover of constituent cells. To sustain the continuously, it’s essential to preserve ‘old’ tight junctions (TJs) between cells being excluded from and their neighbors simultaneously forming de novo TJs newly adjacent However, molecular mechanisms involved in formation remain largely unknown. This study investigates two scenarios: during removal apoptotic monolayer sheets differentiation granular layer stratified epidermis. We revealed that rapid claudin assembly is achieved by actively regulating dissociation EpCAM/TROP2-claudin complex both situations. Furthermore, we found Rho-ROCK pathway initiates activation matriptase, which cleaves EpCAM/TROP2, resulting supply polymerizable stockpiled at plasma membrane induce TJ formation.

Язык: Английский

Процитировано

1
Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity DOI Creative Commons
Elodie Ehret,

Sévan Stroh,

Muriel Auberson

и другие.

Cells, Год журнала: 2023, Номер 12(19), С. 2342 - 2342

Опубликована: Сен. 23, 2023

The serine proteases CAP1/Prss8 and CAP3/St14 are identified as ENaC channel-activating in vitro, highly suggesting that they required for proteolytic activation of vivo. present study tested whether is relevant renal affects ENaC-mediated Na+ absorption following deprivation conditions. knockout mice exhibit a significant decrease protein expression with altered subunit decreased pNCC abundances but overall maintain sodium balance. RNAscope-based analyses reveal co-expression alpha distal tubules the cortex from wild-type mice. Double CAP1/Prss8; CAP3/St14-deficiency maintained K+ balance on Na+-deprived diet, restored showed reduced NCC activity under deprivation. Overall, our data clearly show not direct its abundance. Our reveals complex regulation by these level rather than activation.

Язык: Английский

Процитировано

3
Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity DOI Open Access
Elodie Ehret,

Sévan Stroh,

Muriel Auberson

и другие.

Опубликована: Авг. 14, 2023

The serine proteases CAP1/Prss8 (prostasin) and CAP3/St14 (matriptase) are identified as ENaC channel-activating in vitro highly suggesting that they required for proteolytic activation of vivo. present study tested whether CAP3 is relevant renal affects ENaC-mediated Na+ absorption following Na+-deprivation conditions. knockout mice exhibit significant decrease CAP1 protein expression with altered subunit decreased pNCC abundances, but overall maintain sodium balance. RNAscope-based analyses reveal co-expression alpha distal tubules the cortex from wildtype mice. Double CAP1/CAP3-deficiency maintained K+ balance on Na+-deprived diet, restored abundances showed reduced NCC activity under Na+-deprivation. Overall, our data clearly show not direct ENaC, its abundances. Our a complex regulation by these level rather than activation.

Язык: Английский

Процитировано

2
Claudin-4 polymerizes after the incorporation of just two extracellular claudin-3 residues DOI Creative Commons
Rozemarijn E. van der Veen, Jörg Piontek,

Marie Bieck

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 15, 2023

Abstract Tight junctions play a pivotal role in the functional integrity of human body by forming barriers crucial for tissue compartmentalization and protecting from external threats. Essential components tight are transmembrane claudin proteins, which can polymerize into junction strands meshworks. This study delves structural determinants polymerization, utilizing close homology yet strong difference polymerization capacity between claudin-3 claudin-4. Through combination sequence alignment modeling, critical residues second extracellular segment pinpointed. Molecular dynamics simulations provide insights interactions conformational changes induced identified 2 residues, shedding light on intricacies polymerization. Live-STED imaging demonstrates that introduction these claudin-4 significantly enhances non-epithelial cells. In junction-deficient epithelial cells, mutated not only influences morphology but also partially restores barrier function. Understanding basis is paramount importance, as it offers dynamic nature junctions. knowledge could be applied to targeted therapeutic interventions, offering insight repair or prevent defects associated with pathological conditions, introduce temporary openings during drug delivery.

Язык: Английский

Процитировано

2
Matrix metalloproteinase-7 and claudin-7 as novel identified therapeutic targets for restoration of intestinal epithelial barrier in inflammatory bowel diseases DOI

Sunisa Hankan,

Pawin Pongkorpsakol

Tissue Barriers, Год журнала: 2023, Номер 12(1)

Опубликована: Фев. 18, 2023

Intestinal tight junction disruption and mucosal immune dysregulation contribute to pathogenesis progression of inflammatory bowel diseases (IBD). A proteolytic enzyme matrix metalloproteinase 7 (MMP-7), which is highly expressed in intestinal tissue, implicated IBD other overactivation-associated diseases. In the issue Frontiers Immunology, Ying Xiao colleagues demonstrate that MMP-7-mediated claudin-7 degradation promotes disease progression. Therefore, inhibition MMP-7 enzymatic activity can be a therapeutic strategy for treatment IBD.

Язык: Английский

Процитировано

1
Early-onset tufting enteropathy in HAI-2-deficient mice is independent of matriptase-mediated cleavage of EpCAM DOI Creative Commons
Roman Szabo, Makiko Kawaguchi, Hiroaki Kataoka

и другие.

Development, Год журнала: 2023, Номер 150(17)

Опубликована: Авг. 4, 2023

Congenital tufting enteropathy (CTE) is a life-threatening intestinal disorder resulting from loss-of-function mutations in EPCAM and SPINT2. Mice deficient Spint2, encoding the protease inhibitor HAI-2, develop CTE-like failure associated with progressive loss of EpCAM protein, which caused by unchecked activity serine matriptase (ST14). Here, we show that HAI-2 leads to increased proteolytic processing EpCAM. Elimination reported cleavage site strongly suppressed vitro vivo. Unexpectedly, expression cleavage-resistant failed prevent postnatal lethality Spint2-deficient mice. In addition, genetic inactivation (St14) counteracted effect Spint2 deficiency mice expressing EpCAM, indicating does not drive dysfunction excessive proteolysis Interestingly, developed late-onset defects exhibited shortened lifespan even presence suggesting indispensable for function. Our findings provide new insights into role etiology enteropathies driven deficiency.

Язык: Английский

Процитировано

1
Loss of intermicrovillar adhesion impairs basolateral junctional complexes in transporting epithelia DOI Creative Commons

Caroline S. Cencer,

Kianna L. Robinson,

Matthew J. Tyska

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 19, 2024

Transporting epithelial cells in the gut and kidney rely on protocadherin-based apical adhesion complexes to organize microvilli that extend into luminal space. In these systems, CDHR2 CDHR5 localize distal ends of microvilli, where they form an intermicrovillar complex (IMAC) links tips structures, promotes formation a well-ordered array protrusions, turn maximizes membrane surface area. Recently, we discovered IMACs can also between from neighboring cells, across cell-cell junctions. As additional point physical contact transjunctional are well positioned impact integrity canonical tight adherens junctions more basolaterally. Here, sought test this idea using cell culture mouse models lacked expression were unable IMACs. knockout perturbed junction morphology, led loss key components junctions, impaired barrier function wound healing. These results indicate that, addition organizing provide layer functions parallel with support physiological transporting epithelia.

Язык: Английский

Процитировано

0