Assembly of Tight Junction Strands: Claudin-10b and Claudin-3 Form Homo-Tetrameric Building Blocks that Polymerise in a Channel-Independent Manner

Hempel, Caroline; Protze, Jonas; Altun, E.; Riebe, B.; Piontek, Anna; Fromm, Anja; Lee, I.M.; Saleh, Tarek M.; Günzel, Dorothee; Krause, Gerd; Piontek, Jörg

doi:10.1016/j.jmb.2020.02.034

Cited by 33 publications

(108 citation statements)

References 44 publications

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“…However, also TJ may serve as a signal transducing structure. Claudins establish trans-interactions with claudins of adjacent cells, and thereby they control paracellular permeability [21]. Those trans-interactions have been demonstrated also for CLDN3 with CLDN1, CLDN3 and CLDN5, and it has been demonstrated that the trans-interaction causes an enrichment of the trans-interacting claudin at the contact site in the membrane of the adjacent cells [48].…”

Section: Discussionmentioning

confidence: 90%

TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei

Schilpp

Lochbaum

Braubach

et al. 2021

Pflugers Arch - Eur J Physiol

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TGF-β1 is a major mediator of airway tissue remodelling during atopic asthma and affects tight junctions (TJs) of airway epithelia. However, its impact on TJs of ciliated epithelia is sparsely investigated. Herein we elaborated effects of TGF-β1 on TJs of primary human bronchial epithelial cells. We demonstrate that TGF-β1 activates TGF-β1 receptors TGFBR1 and TGFBR2 resulting in ALK5-mediated phosphorylation of SMAD2. We observed that TGFBR1 and -R2 localize specifically on motile cilia. TGF-β1 activated accumulation of phosphorylated SMAD2 (pSMAD2-C) at centrioles of motile cilia and at cell nuclei. This triggered an increase in paracellular permeability via cellular redistribution of claudin 3 (CLDN3) from TJs into cell nuclei followed by disruption of epithelial integrity and formation of epithelial lesions. Only ciliated cells express TGF-β1 receptors; however, nuclear accumulations of pSMAD2-C and CLDN3 redistribution were observed with similar time course in ciliated and non-ciliated cells. In summary, we demonstrate a role of motile cilia in TGF-β1 sensing and showed that TGF-β1 disturbs TJ permeability of conductive airway epithelia by redistributing CLDN3 from TJs into cell nuclei. We conclude that the observed effects contribute to loss of epithelial integrity during atopic asthma.

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Section: Discussionmentioning

confidence: 90%

TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei

Schilpp

Lochbaum

Braubach

et al. 2021

Pflugers Arch - Eur J Physiol

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“…In this model, the tight junction permeability barrier is a highly crosslinked three-dimensional macromolecular lattice that forms a redundant steric barrier to paracellular solute movement ( Figure 1 ). The claudins, via cis interactions, form antiparallel double row strands within the plasma membrane (see, e.g., [ 59 , 60 ]). The claudins within these strands interact vis trans interactions with complementary claudins in the claudin strands of apposing cell membranes [ 32 , 61 ].…”

Section: Tight Junction Structurementioning

confidence: 99%

The Epithelial Cell Leak Pathway

Monaco

Ovryn

Axis

et al. 2021

IJMS

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The epithelial cell tight junction structure is the site of the transepithelial movement of solutes and water between epithelial cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, the Pore Pathway mediating the movement of small ions and solutes and the Leak Pathway mediating the movement of large solutes. Claudin proteins form the basic paracellular permeability barrier and mediate the movement of small ions and solutes via the Pore Pathway. The Leak Pathway remains less understood. Several proteins have been implicated in mediating the Leak Pathway, including occludin, ZO proteins, tricellulin, and actin filaments, but the proteins comprising the Leak Pathway remain unresolved. Many aspects of the Leak Pathway, such as its molecular mechanism, its properties, and its regulation, remain controversial. In this review, we provide a historical background to the evolution of the Leak Pathway concept from the initial examinations of paracellular permeability. We then discuss current information about the properties of the Leak Pathway and present current theories for the Leak Pathway. Finally, we discuss some recent research suggesting a possible molecular basis for the Leak Pathway.

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“…These predictions have provided testable models of CLDN self-organization, pore structure and selectivity, and the cis and/or trans interfaces that enable these assemblies and functions. Although some models or portions of them have been verified in vitro and/or in vivo using cross-linking, mutagenesis, freeze-fracture EM, fluorescence confocal microscopy, and FRET (338,341,342), an experimentally derived structural basis for CLDN interactions and assemblies has yet to be elucidated.…”

Section: How Do Ions Cross the Membrane? Insights From Structures Of Ion Channelsmentioning

confidence: 99%

Highlighting membrane protein structure and function: A celebration of the Protein Data Bank

Egea

Vecchio

et al. 2021

Journal of Biological Chemistry

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Assembly of Tight Junction Strands: Claudin-10b and Claudin-3 Form Homo-Tetrameric Building Blocks that Polymerise in a Channel-Independent Manner

Cited by 33 publications

References 44 publications

TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei

TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei

The Epithelial Cell Leak Pathway

Highlighting membrane protein structure and function: A celebration of the Protein Data Bank

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