Molecular organization, regulation and function of tricellular junctions

Higashi, Tomohito; Chiba, Hideki

doi:10.1016/j.bbamem.2019.183143

Cited by 38 publications

(34 citation statements)

References 97 publications

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“…Although tricellulin and occludin have similar domain organization, these proteins are differentially localized. Tricellulin is exclusively localized at tricellular junctions, where three epithelial cells meet (Higashi and Miller, 2017;Higashi and Chiba, 2020), whereas occludin is distributed along bicellular TJ, suggesting that tricellulin and occludin function at tTJs and bicellular TJs, respectively. Previous reports (Ikenouchi et al, 2008;Kitajiri et al, 2014) and our data ( Figure S5) showed that occludin is responsible for the confinement of tricellulin at tricellular contacts.…”

Section: Discussionmentioning

confidence: 99%

“…TJs consist of various transmembrane proteins, such as claudins, TJ-Associated MARVEL (MAL and related proteins for vesicle trafficking and membrane link) Proteins (TAMPs), angulins and Junctional Adhesion Molecules (JAMs) (Chiba et al, 2008;Higashi and Chiba, 2020). Claudins are considered major integral membrane proteins of TJ strands (Furuse et al, 1998a;Piontek et al, 2020) and consist of a protein family of more than 20 members, which are differentially expressed in most epithelial tissues in different combinations.…”

Section: Introductionmentioning

confidence: 99%

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Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function

Saitō

Higashi

Fukazawa

et al. 2021

MBoC

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106

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Tight junctions (TJs) are composed of a claudin-based anastomosing network of TJ strands, at which plasma membranes of adjacent epithelial cells are closely attached to regulate the paracellular permeability. Although the TJ proteins occludin and tricellulin have been known to be incorporated in the TJ strand network, their molecular functions remain unknown. Here, we established tricellulin/occludin-double knockout (dKO) MDCK II cells using a genome editing technique, and evaluated the structure and barrier function of these cells. In freeze-fracture replica electron microscopy, the TJ strands of tricellulin/occludin-dKO cells had fewer branches and were less anastomosed compared with the controls. The paracellular permeability of ions and small tracers was increased in the dKO cells. A single KO of tricellulin or occludin had limited effects on the morphology and permeability of TJs. Mathematical simulation using a simplified TJ strand network model predicted that reduced cross-links in TJ strands lead to increased permeability of ions and small macromolecules. Furthermore, overexpression of occludin increased the complexity of TJ strand network and strengthened barrier function. Taken together, our data suggest that tricellulin and occludin mediate the formation and/or stabilization of TJ strand branching points, and contribute to the maintenance of epithelial barrier integrity. [Media: see text]

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function

Saitō

Higashi

Fukazawa

et al. 2021

MBoC

Self Cite

106

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“…On the one hand, abortive extrusion may be related to the distance that needs to be closed by the neighbouring cells: while this can be short for lines of cells (using the shortest axis), it will be higher for clusters and may prevent fast fusion of neighbouring cell junctions and gap closure 23 . On the other hand, abortive extrusion may be related to caspase-induced remodeling of tricellular junctions 24 , which are shared by caspase positive cells only in the case of clustered eliminations. Interestingly, some tricellular junction components have been shown to be cleaved by caspases 25 .…”

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confidence: 99%

Robustness of epithelial sealing is an emerging property of local ERK feedbacks driven by cell elimination

Valon

Levillayer

Davidović

et al. 2020

Preprint

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10While the pathways regulating apoptosis and cell extrusion are rather well 11 described 1,2 , what regulates the precise spatio-temporal distribution of cell 12 elimination in tissues remains largely unknown. This is particularly relevant for 13 epithelia with high rates of cell elimination, a widespread situation during 14 embryogenesis 3-6 and homeostasis 7 , where concomitant death of neigbours could 15 impair the maintenance of epithelial sealing. However, the extent to which epithelial 16 tissues can cope with concomitant cell death, and whether any mechanism 17 regulates such occurrence have never been explored so far. Here, using the 18 Drosophila pupal notum (a single layer epithelium) and a new optogenetic tool to 19 trigger caspase activation and cell extrusion, we first show that concomitant death 20 of clusters of at least three cells is sufficient to transiently impair epithelial sealing. 21 Such clustered extrusion was almost never observed in vivo, suggesting the 22 existence of a mechanism preventing concomitant elimination of neighbours. 23 Statistical analysis of cell death distribution in the notum highlighted a transient 24 and local protective phase occurring near every dying cell. This protection is driven 25 by a transient activation of ERK in the direct neighbours of extruding cells which 26 reverts caspase activation and prevents elimination of cells in clusters. Altogether, 27 this study demonstrates that the distribution of cell elimination in epithelia is an 28 emerging property of transient and local feedbacks through ERK activation which 29 is required to maintain epithelial sealing in conditions of high rate of cell 30 elimination. 31 Epithelial cell elimination is driven by extrusion, a succession of remodeling steps 32 removing one cell from the epithelial layer while maintaining epithelial sealing 1,8 . We first 33 asked whether concomitant extrusion of several neigbours impairs the maintenance of 34 epithelial sealing. As such, we developed a UAS-optoDronc Drosophila line, which can 35 trigger rapid caspase activation through blue light-induced clustering of Caspase9 36 (Figure 1a, Figure S1a). Expression of optoDronc in fly eyes (GMR-gal4 eye-specific 37 driver) is sufficient to trigger cell death upon blue light exposure and can be rescued by 38 expression of the downstream effector caspase inhibitor p35 (Figure S1b). We then used 39 the Drosophila pupal notum to assess the efficiency of the construct in triggering epithelial 40 cell elimination. Blue light exposure of clones expressing optoDronc triggers elimination 41 of the majority of cells in less than one hour (Figure 1b, Figure S1c,e, movie S1). 42 OptoDronc-triggered extrusions are similar to physiological extrusions in the pupal notum, 43 albeit slightly faster (Figure S1f), and require effector caspase activation (Figure S1d,e, 44 movie S1) like physiological extrusions in the notum 9,10 . We then induced concomitant 45 elimination of group of cells of various sizes and shapes by expressing optoDronc in 46...

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“…The tSJ is composed of unique proteins that include Gliotactin (Gli) [10], Bark Beetle (also known as Anakonda) [11,12], and M6 [13]. Readers interested in the organization and biogenesis of the tSJ are directed to the review by Higashi and Chiba [14], and recent papers by Esmangart de Bournonville [15] and Wittek [16].…”

Section: Structure and Composition Of Sjsmentioning

confidence: 99%

Expanding the Junction: New Insights into Non-Occluding Roles for Septate Junction Proteins during Development

Rice

Alhadyian

et al. 2021

JDB

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The septate junction (SJ) provides an occluding function for epithelial tissues in invertebrate organisms. This ability to seal the paracellular route between cells allows internal tissues to create unique compartments for organ function and endows the epidermis with a barrier function to restrict the passage of pathogens. Over the past twenty-five years, numerous investigators have identified more than 30 proteins that are required for the formation or maintenance of the SJs in Drosophila melanogaster, and have determined many of the steps involved in the biogenesis of the junction. Along the way, it has become clear that SJ proteins are also required for a number of developmental events that occur throughout the life of the organism. Many of these developmental events occur prior to the formation of the occluding junction, suggesting that SJ proteins possess non-occluding functions. In this review, we will describe the composition of SJs, taking note of which proteins are core components of the junction versus resident or accessory proteins, and the steps involved in the biogenesis of the junction. We will then elaborate on the functions that core SJ proteins likely play outside of their role in forming the occluding junction and describe studies that provide some cell biological perspectives that are beginning to provide mechanistic understanding of how these proteins function in developmental contexts.

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Molecular organization, regulation and function of tricellular junctions

Cited by 38 publications

References 97 publications

Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function

Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function

Robustness of epithelial sealing is an emerging property of local ERK feedbacks driven by cell elimination

Expanding the Junction: New Insights into Non-Occluding Roles for Septate Junction Proteins during Development

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