Claudin Tight Junction Proteins: Novel Aspects in Paracellular Transport

2008 ◽  
Vol 28 (6) ◽  
pp. 577-584 ◽  
Author(s):  
Constanze Will ◽  
Michael Fromm ◽  
Dominik Müller
Keyword(s):  
Tight Junction ◽  
Solute Transport ◽  
Molecular Mechanisms ◽  
Family Members ◽  
Transport Processes ◽  
Paracellular Transport ◽  
Solute Flux ◽  
Solute Fluxes ◽  
Essential Components ◽  
Renal Tubular

Claudins are essential components of the intercellular tight junction and major determinants of paracellular solute fluxes across epithelia and endothelia. Many members of this family display a distinct charge or size specificity, whereas others render the epithelium impermeable to transport. Due to intercellular localization, claudin-mediated transport processes are passive and driven by an electrochemical gradient. In epithelial tissues, claudins exhibit a temporal–spatial expression pattern corresponding with regional and local solute transport profiles. Whereas paracellular transport mechanisms in organs such as intestine and kidney have been extensively investigated, little is known about the molecular mechanisms determining solute transport in the peritoneum, and thus the determinants of peritoneal dialysis. Given the ubiquitous expression of claudins in endothelia and epithelia, it is predictable that claudins also contribute to pore formation and determination in the peritoneum, and that they are involved in solute flux. Therefore, we review the basic characteristics of claudin family members and their function as exemplified in renal tubular transport and give an outlook to what extent claudin family members might be of importance for solute reabsorption across the peritoneal membrane.

Claudins at the gate: determinants of renal epithelial tight junction paracellular permeability

2006 ◽  
Vol 290 (3) ◽  
pp. F572-F579 ◽  
Author(s):  
Daniel F. Balkovetz
Keyword(s):  
Tight Junction ◽  
Membrane Lipids ◽  
Expression Patterns ◽  
Large Family ◽  
Paracellular Permeability ◽  
Paracellular Transport ◽  
Renal Epithelial Cell ◽  
Culture Models ◽  
Epithelial Tight Junction ◽  
Renal Tubular

The epithelial tight junction (TJ) is responsible for the control of paracellular transport between epithelial cells (gate function) and the maintenance of apical/basolateral polarity by preventing the diffusion of membrane lipids and/or proteins from one surface domain to another (fence function). Renal tubule epithelia in the mammalian nephron have TJs that determine paracellular transport characteristics. Paracellular transport across renal tubular epithelial TJs (gate function) varies in different segments of the nephron. A large family of recently identified TJ-associated transmembrane proteins named claudins appear to determine the paracellular permeability properties of the TJ. A combination of inherited human diseases, renal epithelial cell culture models, and nephron expression patterns of claudins is providing important clues about how claudin molecules determine the TJ gate function of renal epithelia in different segments of the nephron.

scholarly journals An effective parameterization to quantify multiple solute flux breakthrough curves

2014 ◽  
Vol 11 (6) ◽  
pp. 6993-7017
Author(s):  
E. Bloem ◽  
M. de Gee ◽  
G. H. de Rooij
Keyword(s):  
Solute Transport ◽  
Flux Density ◽  
Breakthrough Curves ◽  
Solute Flux ◽  
Spatial Effects ◽  
Solute Fluxes ◽  
Spatial Aspect ◽  
Temporal Aspect ◽  
Temporal And Spatial ◽  
The Individual

Abstract. To understand soil and groundwater contamination we study the temporal and spatial aspects of solute transport in the unsaturated zone. One monitoring instrument that captures both aspects is the multi-compartment sampler (MCS). With the MCS developed by Bloem et al. (2010) we are able to measure the downward solute fluxes in 100 compartments at the depth of installation of the MCS, with a minimal disturbance of the flow field. Over time this dataset results in 100 individual solute flux breakthrough curves (BTCs) (temporal aspect). Sorting the BTCs in descending order of solute mass gives the spatial solute distribution curve (spatial aspect). We present a method to quantitatively characterize datasets gathered with MCS (or single samplers installed at multiple locations in a field at the same depth). The method approximates the full set of breakthrough curves using only a single function with four to eight parameters, which combines both temporal and spatial effects of solute transport in soils. This is achieved by modeling the scaled solute flux density breakthrough curves (BTCF) for each compartment as the solution of a conventional one-dimensional equilibrium convection disperion equation (CDE), without modifications. We detect and parameterize any relationships between the resulting transport velocities and dispersion coefficients of the individual BTCFs. Finally the spatial aspect is parameterized using the Beta distribution. This method is based on the flux density BTCs directly, which for transport phenomena is preferred over solute concentrations. In three experiments on undisturbed soils, the resulting approximation matched the data well.

scholarly journals Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury

2009 ◽  
Vol 297 (2) ◽  
pp. L219-L227 ◽  
Author(s):  
Charlie Wray ◽  
Ying Mao ◽  
Jue Pan ◽  
Anita Chandrasena ◽  
Frank Piasta ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Tight Junction ◽  
Pulmonary Edema ◽  
Barrier Function ◽  
Mapk Pathway ◽  
Paracellular Transport ◽  
Epithelial Barrier ◽  
Altered Expression ◽  
Alveolar Epithelial

Intact alveolar barrier function is associated with better outcomes in acute lung injury patients; however, the regulation of alveolar epithelial paracellular transport during lung injury has not been extensively investigated. This study was undertaken to determine whether changes in tight junction claudin expression affect alveolar epithelial barrier properties and to determine the mechanisms of altered expression. In anesthetized mice exposed to ventilator-induced lung injury, claudin-4 was specifically induced among tight junction structural proteins. Real-time PCR showed an eightfold increase in claudin-4 expression in the lung injury model. To examine the role of this protein in barrier regulation, claudin-4 function was inhibited with small interfering RNA (siRNA) and a blocking peptide derived from the binding domain of Clostridium perfringens enterotoxin (CPEBD). Inhibition of claudin-4 decreased transepithelial electrical resistance but did not alter macromolecule permeability in primary rat and human epithelial cells. In mice, CPEBD decreased air space fluid clearance >33% and resulted in pulmonary edema during moderate tidal volume ventilation that did not induce edema in control peptide-treated mice. In vitro phorbol ester induced a ninefold increase in claudin-4 expression that was dependent on PKC activation and the JNK MAPK pathway. These data establish that changes in alveolar epithelial claudin expression influence paracellular transport, alveolar fluid clearance rates, and susceptibility to pulmonary edema. We hypothesize that increased claudin-4 expression early in acute lung injury represents a mechanism to limit pulmonary edema and that the regulation of alveolar epithelial claudin expression may be a novel target for acute lung injury therapy.

Role of membrane trafficking in plasma membrane solute transport

1994 ◽  
Vol 267 (1) ◽  
pp. C1-C24 ◽  
Author(s):  
N. A. Bradbury ◽  
R. J. Bridges
Keyword(s):  
Plasma Membrane ◽  
Solute Transport ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Water Channel ◽  
Transport Proteins ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Regulated Trafficking

Cells can rapidly and reversibly alter solute transport rates by changing the kinetics of transport proteins resident within the plasma membrane. Most notably, this can be brought about by reversible phosphorylation of the transporter. An additional mechanism for acute regulation of plasma membrane transport rates is by the regulated exocytic insertion of transport proteins from intracellular vesicles into the plasma membrane and their subsequent regulated endocytic retrieval. Over the past few years, the number of transporters undergoing this regulated trafficking has increased dramatically, such that what was once an interesting translocation of a few transporters has now become a widespread modality for regulating plasma membrane solute permeabilities. The aim of this article is to review the models proposed for the regulated trafficking of transport proteins and what lines of evidence should be obtained to document regulated exocytic insertion and endocytic retrieval of transport proteins. We highlight four transporters, the insulin-responsive glucose transporter, the antidiuretic hormone-responsive water channel, the urinary bladder H(+)-ATPase, and the cystic fibrosis transmembrane conductance regulator Cl- channel, and discuss the various approaches taken to document their regulated trafficking. Finally, we discuss areas of uncertainty that remain to be investigated concerning the molecular mechanisms involved in regulating the trafficking of proteins.

Genetic analysis of intracellular aminoglycerophospholipid traffic

2004 ◽  
Vol 82 (1) ◽  
pp. 156-169 ◽  
Author(s):  
Dennis R Voelker
Keyword(s):  
Genetic Analysis ◽  
Mammalian Cells ◽  
Molecular Genetic ◽  
Family Members ◽  
Molecular Genetic Analysis ◽  
Transport Processes ◽  
Membrane Biogenesis ◽  
Independent Manner ◽  
Multiple Genes ◽  
Vacuolar Protein

Inter- and intramembrane phospholipid transport processes are central features of membrane biogenesis and homeostasis. Relatively recent successes in the molecular genetic analysis of aminoglycerophospholipid transport processes in both yeast and mammalian cells are now providing important new information defining specific protein and lipid components that participate in these reactions. Studies focused on phosphatidylserine (PtdSer) transport to the mitochondria reveal that the process is regulated by ubiquitination. In addition, a specific mutation disrupts PtdSer transport between mitochondrial membranes. Analysis of PtdSer transport from the endoplasmic reticulum to the locus of PtdSer decarboxylase 2 demonstrates the requirement for a phosphatidylinositol-4-kinase, a phosphatidylinositol-binding protein, and the C2 domain of the decarboxylase. Examination of NBD-phosphatidylcholine transport demonstrates the involvement of the prevacuolar compartment and a requirement for multiple genes involved in regulating vacuolar protein sorting for transport of the lipid to the vacuole. In intramembrane transport, multiple genes are now identified including those encoding multidrug resistant protein family members, DNF family members, ATP binding cassette transporters, and pleiotropic drug resistance family members. The scramblase family constitutes a collection of putative transmembrane transporters that function in an ATP-independent manner. The genetic analysis of lipid traffic is uncovering new molecules involved in all aspects of the regulation and execution of the transport steps and also providing essential tools to critically test the involvement of numerous candidate molecules.Key words: lipid transport, lipid sorting, membrane biogenesis, organelles, flippase.

scholarly journals MicroRNA-277 targetsinsulin-like peptides 7and8to control lipid metabolism and reproduction inAedes aegyptimosquitoes

2017 ◽  
Vol 114 (38) ◽  
pp. E8017-E8024 ◽  
Author(s):  
Lin Ling ◽  
Vladimir A. Kokoza ◽  
Changyu Zhang ◽  
Emre Aksoy ◽  
Alexander S. Raikhel
Keyword(s):  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Critical Role ◽  
Target Prediction ◽  
Luciferase Reporter ◽  
Ovary Development ◽  
Mrna Levels ◽  
Essential Components ◽  
Energy Store

Hematophagous female mosquitoes transmit numerous devastating human diseases, including malaria, dengue fever, Zika virus, and others. Because of their obligatory requirement of a vertebrate blood meal for reproduction, these mosquitoes need a lot of energy; therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. Lipids are the major energy store providing the fuel required for host seeking and reproduction. They are essential components of the fat body, a metabolic tissue that is the insect analog of vertebrate liver and adipose tissue. In this study, we found that microRNA-277 (miR-277) plays an important role in regulating mosquito lipid metabolism. The genetic disruption of miR-277 using the CRISPR-Cas9 system led to failures in both lipid storage and ovary development. miR-277 mimic injection partially rescued these phenotypic manifestations. Examination of subcellular localization of FOXO protein via CRISPR-assisted, single-stranded oligodeoxynucleotide-mediated homology-directed repair revealed that insulin signaling is up-regulated in response to miR-277 depletion. In silico target prediction identified that insulin-like peptides 7 and 8 (ilp7andilp8) are putative targets of miR-277; RNA immunoprecipitation and a luciferase reporter assay confirmed thatilp7andilp8are direct targets of this miRNA. CRISPR-Cas9 depletion ofilp7andilp8led to metabolic and reproductive defects. These depletions identified differential actions of ILP7 and ILP8 in lipid homeostasis and ovarian development. Thus, miR-277 plays a critical role in mosquito lipid metabolism and reproduction by targetingilp7andilp8, and serves as a monitor to control ILP7 and ILP8 mRNA levels.

scholarly journals Arabinogalactan Proteins in Plant Roots – An Update on Possible Functions

2021 ◽  
Vol 12 ◽  
Author(s):  
Dagmar Hromadová ◽  
Aleš Soukup ◽  
Edita Tylová
Keyword(s):  
Cell Wall ◽  
Regulatory Networks ◽  
Developmental Plasticity ◽  
Molecular Mechanisms ◽  
Arabinogalactan Proteins ◽  
Cellular Level ◽  
Environmental Response ◽  
Essential Components ◽  
Surface Signaling ◽  
Cell Surface Signaling

Responsiveness to environmental conditions and developmental plasticity of root systems are crucial determinants of plant fitness. These processes are interconnected at a cellular level with cell wall properties and cell surface signaling, which involve arabinogalactan proteins (AGPs) as essential components. AGPs are cell-wall localized glycoproteins, often GPI-anchored, which participate in root functions at many levels. They are involved in cell expansion and differentiation, regulation of root growth, interactions with other organisms, and environmental response. Due to the complexity of cell wall functional and regulatory networks, and despite the large amount of experimental data, the exact molecular mechanisms of AGP-action are still largely unknown. This dynamically evolving field of root biology is summarized in the present review.

scholarly journals Changes in porcine nutrient transport physiology in response to Ascaris suum infection

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sarina Koehler ◽  
Andrea Springer ◽  
Nicole Issel ◽  
Stefanie Klinger ◽  
Christina Strube ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ascaris Suum ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Nutrient Transport ◽  
Transport Processes ◽  
Infected Group ◽  
Peptide Transporter ◽  
Control Group ◽  
Expression Levels

Abstract Background The roundworm Ascaris suum is one of the parasites with the greatest economic impact on pig farming. In this context, lower weight gain is hypothesized to be due to decreased nutrient absorption. This study aims at characterizing the effects of A. suum infection on intestinal nutrient transport processes and potential molecular mechanisms. Methods Three groups of six piglets each were infected orally (10,000 embryonated A. suum eggs) in a single dose (“single infection”). Another three groups were infected orally (1000 embryonated eggs) for 10 consecutive days (“trickle infection”). Animals were necropsied 21, 35 and 49 days post-infection (dpi). Three groups served as respective controls. The Ussing chamber technique was applied for the functional characterization of small intestinal tissues [short-circuit currents (Isc) as induced by glucose, alanine and peptides; 3H-glucose net flux rates; tissue conductance (Gt)]. Transcription and expression levels of relevant cytokines and nutrient transporters were evaluated (qPCR/western blot). Results Peptide- and alanine-induced changes in Isc were significantly decreased in the jejunum and ileum of the trickle-infected group at 49 dpi and in the ileum of the single-infected group at 49 dpi. No significant differences regarding glucose transport were observed between the Ascaris-infected groups and the control group in Ussing chamber experiments. Transcription levels of the glucose and peptide transporters as well as of selected transcription factors (transcription of signal transducer and activator of transcription 6 [STAT6] and hypoxia-inducible factor 1-alpha [Hif-1α]) were significantly increased in response to both infection types after some periods. The transcription of interleukins 4 and 13 varied between decrease and increase regarding the respective time points, as did the protein expression of glucose transporters. The expression of the peptide transporter PepT1 was significantly decreased in the ileal single-infected group at 35 dpi. Hif-1α was significantly increased in the ileal tissue from the single-infected group at 21 dpi and in the trickle-infected group at 35 dpi. The expression levels of Na+/K+-ATPase and ASCT1 remained unaffected. Conclusions In contrast to the current hypothesis, these results indicate that the nutrient deprivation induced by A. suum cannot be explained by transcriptional or expression changes alone and requires further studies. Graphical abstract

Sign in / Sign up

Export Citation Format

Share Document