The emergence of the concept of tight junctions and physiological regulation by ouabain

Larre, Isabel; Ponce, Arturo; Franco, Martha; Cereijido, Marcelino

doi:10.1016/j.semcdb.2014.09.010

Cited by 9 publications

(8 citation statements)

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“…The physiological properties of the junctional gate are that of a semipermeable diffusion barrier that discriminates solutes on the basis of size and charge 72 . Solutes can cross the junctional paracellular pathway along two routes.…”

Section: Regulation Of Paracellular Permeabilitymentioning

confidence: 99%

“…These pores have a diameter of ~4-8Å depending tissue and molecule analysed [73][74][75] . A second diffusion pathway allows the diffusion of larger solutes, macromolecules up to a size limit of ~30-60Å 72,75 . Charge-selective ion permeation and size-selective macromolecular diffusion occur by different mechanisms and can be regulated in opposing manners 76 .…”

Section: Regulation Of Paracellular Permeabilitymentioning

confidence: 99%

See 1 more Smart Citation

Tight junctions: from simple barriers to multifunctional molecular gates

Zihni

Mills

Matter

et al. 2016

Nat Rev Mol Cell Biol

1,078

925

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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: Regulation Of Paracellular Permeabilitymentioning

confidence: 99%

Section: Regulation Of Paracellular Permeabilitymentioning

confidence: 99%

Tight junctions: from simple barriers to multifunctional molecular gates

Zihni

Mills

Matter

et al. 2016

Nat Rev Mol Cell Biol

1,078

925

View full text Add to dashboard Cite

show abstract

“…In contrast to the studies cited above, Larre and co-workers reported that three-day incubation of MDCK cells with ouabain at concentrations 10–50 nM does not disturb [K + ] i , but increases the hermeticity of the tight junctions measured by transepithelial electrical and increases gap junctional communication between the cells [ 65 , 66 ] suggesting the implication of Na + i ,K + i -independent signaling pathways [ 54 , 67 ]. Using pharmacological approaches, it was shown that these phenomena might be mediated by an ~2-fold elevation of c-Src and ERK1/2 MAPK phosphorylation [ 68 ]. Thus, additional experiments should be performed to examine the relative impact of Na + i ,K + i -mediated and -independent signaling in the maintenance of tight junction and cell adhesion.…”

Section: Evidence For Na + I K mentioning

confidence: 99%

Na+i,K+i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids: Facts and Artifacts

et al. 2017

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Na+,K+-ATPase is the only known receptor of cardiotonic steroids (CTS) whose interaction with catalytic α-subunits leads to inhibition of this enzyme. As predicted, CTS affect numerous cellular functions related to the maintenance of the transmembrane gradient of monovalent cations, such as electrical membrane potential, cell volume, transepithelial movement of salt and osmotically-obliged water, symport of Na+ with inorganic phosphate, glucose, amino acids, nucleotides, etc. During the last two decades, it was shown that side-by-side with these canonical Na+i/K+i-dependent cellular responses, long-term exposure to CTS affects transcription, translation, tight junction, cell adhesion and exhibits tissue-specific impact on cell survival and death. It was also shown that CTS trigger diverse signaling cascades via conformational transitions of the Na+,K+-ATPase α-subunit that, in turn, results in the activation of membrane-associated non-receptor tyrosine kinase Src, phosphatidylinositol 3-kinase and the inositol 1,4,5-triphosphate receptor. These findings allowed researchers to propose that endogenous CTS might be considered as a novel class of steroid hormones. We focus our review on the analysis of the relative impact Na+i,K+i-mediated and -independent pathways in cellular responses evoked by CTS.

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“…The permeability of the tight junctions is determined by composition of proteins, adhesion molecules, intracellular scaffold proteins, and their phosphorylation status 123,124 . Tight junctions discriminate molecules based on size and charge, similar to a semipermeable membrane 125,126 . In contrast to lipophilic substrates and gases, which can penetrate the seminiferous tubule through the cells (e.g., O 2 ), hydrophilic molecules, such as glucose and potassium, must be either transported actively or through facilitated diffusion, respectively 127 …”

Section: Metabolism In the Adult Seminiferous Epitheliummentioning

confidence: 99%

“…123,124 Tight junctions discriminate molecules based on size and charge, similar to a semipermeable membrane. 125,126 In contrast to lipophilic substrates and gases, which can penetrate the seminiferous tubule through the cells (e.g., O 2 ), hydrophilic molecules, such as glucose and potassium, must be either transported actively or through facilitated diffusion, respectively. 127 Both the Sertoli cell junctions and polarity complexes are more basally located in Sertoli cells, in contrast to other epithelial cells.…”

Section: Significance Of the Sertoli Cell Polarization And Blood-test...mentioning

confidence: 99%

Comparing the adult and pre‐pubertal testis: Metabolic transitions and the change in the spermatogonial stem cell metabolic microenvironment

2023

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Background Survivors of childhood cancer often suffer from infertility. While sperm cryopreservation is not feasible before puberty, the patient's own spermatogonial stem cells could serve as a germ cell reservoir, enabling these patients to father their own children in adulthood through the isolation, in vitro expansion, and subsequent transplantation of spermatogonial stem cells. However, this approach requires large numbers of stem cells, and methods for successfully propagating spermatogonial stem cells in the laboratory are yet to be established for higher mammals and humans. The improvement of spermatogonial stem cell culture requires deeper understanding of their metabolic requirements and the mechanisms that regulate metabolic homeostasis. Aim This review gives a summary on our knowledge of spermatogonial stem cell metabolism during maintenance and differentiation and highlights the potential influence of Sertoli cell and stem cell niche maturation on spermatogonial stem cell metabolic requirements during development. Results and conclusions Fetal human spermatogonial stem cell precursors, or gonocytes, migrate into the seminiferous cords and supposedly mature to adult stem cells within the first year of human development. However, the spermatogonial stem cell niche does not fully differentiate until puberty, when Sertoli cells dramatically rearrange the architecture and microenvironment within the seminiferous epithelium. Consequently, pre‐pubertal and adult spermatogonial stem cells experience two distinct niche environments potentially affecting spermatogonial stem cell metabolism and maturation. Indeed, the metabolic requirements of mouse primordial germ cells and pig gonocytes are distinct from their adult counterparts, and novel single‐cell RNA sequencing analysis of human and porcine spermatogonial stem cells during development confirms this metabolic transition. Knowledge of the metabolic requirements and their changes and regulation during spermatogonial stem cell maturation is necessary to implement laboratory‐based techniques and enable clinical use of spermatogonial stem cells. Based on the advancement in our understanding of germline metabolism circuits and maturation events of niche cells within the testis, we propose a new definition of spermatogonial stem cell maturation and its amendment in the light of metabolic change.

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The emergence of the concept of tight junctions and physiological regulation by ouabain

Cited by 9 publications

References 51 publications

Tight junctions: from simple barriers to multifunctional molecular gates

Tight junctions: from simple barriers to multifunctional molecular gates

Na+i,K+i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids: Facts and Artifacts

Comparing the adult and pre‐pubertal testis: Metabolic transitions and the change in the spermatogonial stem cell metabolic microenvironment

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