In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization

Cording, Jimmi; Berg, Johanna; Käding, Nadja; Bellmann, Christian; Tscheik, Christian; Westphal, Julie K.; Milatz, Susanne; Günzel, Dorothee; Wolburg, Hartwig; Piontek, Jörg; Huber, Otmar; Blasig, Ingolf E.

doi:10.1242/jcs.114306

Cited by 153 publications

(183 citation statements)

References 41 publications

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“…This model is supported by the observation that native tight junction strands seem to contain protein and phospholipids 62,63 . According to this model, lipids are filling the gaps between different types of membrane proteins, eliminating the need of proteins forming continuous polymers 58,64 . Consequently, this model enables to explain why different protein components that have different dynamic properties can be a part of the same strands.…”

Section: Models Of Tight Junction Structurementioning

confidence: 99%

Tight junctions: from simple barriers to multifunctional molecular gates

Zihni

Mills

Matter

et al. 2016

Nat Rev Mol Cell Biol

1,020

844

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Main body of text: 5983 words 2Epithelia and endothelia separate different tissue compartments and protect multicellular organisms form the outside world. This requires the formation of tight junctions, selective gates that control paracellular diffusion of ions and solutes. Tight junctions also form the border between the apical and basolateral plasma membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to tight junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Here, we discuss recent advances in our understanding of the molecular architecture and cellular functions of tight junctions.Microscopists in the 19 th century described the paracellular space between neighbouring cells within an epithelial sheet to be sealed by a "terminal bar", a structure later resolved by electron microscopy into a composite of distinct cell-cell junctions that is now called the epithelial junctional complex and is formed by tight junctions, adherens junctions and desmosomes 1,2 . As the former two junctions are more tightly associated and often reside at the apical end of the lateral membrane, they are often referred to as the apical junctional complex (however, in endothelia, tight junctions and adherens junctions can be intercalated) (Fig. 1). Tight junctions are essential for barrier formation, and their primary physiological role is to function as paracellular gates that restrict diffusion on the basis of size and charge. Selective paracellular diffusion is an essential process for the maintenance of homoeostasis in organs and tissues. Tight junctions have long been the most enigmatic of all adhesion complexes and eluded a detailed molecular and functional analysis due to their complex architecture. Recent years have witnessed the identification of a large array of components associated with tight junctions implicating these junctions in an unexpected range of different functions, thereby challenging the traditional model, in which tight junctions are considered a simple diffusion barrier formed by a rigid molecular complex. In line with these various functions, mutations in genes encoding tight junction proteins have been linked to a range of inherited human diseases. Additionally, tight junction components are known to be targeted by a number of pathogenic bacteria and viruses, which hijack tight junction proteins to enter and infect cells, or target junctional signalling mechanisms to cross tissue barriers. Although tight junctions are a vertebrate junction, many of their components and functions are evolutionarily conserved (Box 1).The main purpose of this review is to examine the recent advances in the unravelling of the molecular architecture of tight junctions and understanding their functions. We will discuss recent exciting insights into how tight junctions function as signalling platforms that guide cell behaviour and differen...

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Section: Models Of Tight Junction Structurementioning

confidence: 99%

Tight junctions: from simple barriers to multifunctional molecular gates

Zihni

Mills

Matter

et al. 2016

Nat Rev Mol Cell Biol

1,020

844

View full text Add to dashboard Cite

show abstract

“…Tight junctions are complex protein structures that consist of transmembrane proteins such as claudin, occludin, and tricullulin (Cording et al, 2013). These transmembrane proteins connect with the opposing plasma membrane, thereby forming a mechanical link between epithelial cells and establishing a barrier to paracellular.…”

Section: Microbes Gut Barrier and Inflammationmentioning

confidence: 99%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

183

110

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There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.

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“…Compatible with this theory, knockdown of tricellulin in Eph4 cells rendered bicellular junctions discontinuous (7). Molecular interaction assays revealed that tricellulin could cisinteract with claudins to facilitate the anchoring of bTJ onto tTJ (29). It is not known whether ILDR1 may interact with claudins: e.g., claudin-2 to regulate their permeabilities.…”

Section: Discussionmentioning

confidence: 99%

ILDR1 is important for paracellular water transport and urine concentration mechanism

Gong

Himmerkus

Sunq

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Whether the tight junction is permeable to water remains highly controversial. Here, we provide evidence that the tricellular tight junction is important for paracellular water permeation and that Iglike domain containing receptor 1 (ILDR1) regulates its permeability. In the mouse kidney, ILDR1 is localized to tricellular tight junctions of the distal tubules. Genetic knockout of Ildr1 in the mouse kidney causes polyuria and polydipsia due to renal concentrating defects. Microperfusion of live renal distal tubules reveals that they are impermeable to water in normal animals but become highly permeable to water in Ildr1 knockout animals whereas paracellular ionic permeabilities in the Ildr1 knockout mouse renal tubules are not affected. Vasopressin cannot correct paracellular water loss in Ildr1 knockout animals despite normal effects on the transcellular aquaporin-2-dependent pathway. In cultured renal epithelial cells normally lacking the expression of Ildr1, overexpression of Ildr1 significantly reduces the paracellular water permeability. Together, our study provides a mechanism of how cells transport water and shows how such a mechanism may be exploited as a therapeutic approach to maintain water homeostasis.T ight junctions (TJs) are known to be leaky to ions and, thus, to constitute a paracellular pathway with ionic permselectivity similar to that of transmembrane channels (1). Whether the TJ is permeable to water, on the other hand, has been highly controversial. Jorge Fischbarg noticed that the corneal endothelium retained over 60% of water permeability even when AQP1, the only aquaporin expressed by these cells, was knocked out by genetic deletion (2). Rosenthal et al. have demonstrated that, in cultured renal epithelium expressing the claudin-2 protein, transepithelial water permeability was significantly higher than in cells without its expression (3). Using an optical microscopic approach, Spring and coworkers have directly measured the velocity of water flow across the tight junction and have ruled out the existence of any significant transjunctional water flow, at least for the bicellular TJ (bTJ) (4). The tricellular tight junction (tTJ) is a specialized cell junction different in ultrastructure from that of the bTJ (5). Unlike the bTJ, which is made of claudin and occludin (6), the proteins making the tTJ include tricellulin and angulins (LSR/angulin-1, ILDR1/angulin-2, and ILDR2/angulin-3) (7,8). Transgenic knockout (KO) of either tricellulin or Ildr1 in mice causes hearing loss due to degeneration of mechanosensory cochlear hair cells in the organ of Corti (9, 10). Peculiarly, neither the endocochlear potential nor the paracellular permeability in the stria vascularis changed in these mutant animals. The permeation property of tTJ therefore remains a major mystery.There are two forms of diabetes insipidus (DI): central (neurogenic) and nephrogenic. The nephrogenic DI (NDI) is caused by the inability of the kidney to reabsorb water. NDI is hereditary and has been linked to two genetic loci. The ...

show abstract

In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization

Cited by 153 publications

References 41 publications

Tight junctions: from simple barriers to multifunctional molecular gates

Tight junctions: from simple barriers to multifunctional molecular gates

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

ILDR1 is important for paracellular water transport and urine concentration mechanism

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