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The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens - 1 protein. Gap junctions mediate cell-cell communication in almost all tissues and are composed of channel-forming integral membrane proteins , termed connexins .
Connexin43 Cx43 is the most widely expressed and the most well-studied member of this family. Cxbased cell-cell communication is regulated.
Olfactory receptor signaling is regulated by the post-synaptic density 95, Drosophila discs large, zona-occludens 1 PDZ scaffold multi-PDZ domain protein 1. The unique ability of mammals to detect and discriminate between thousands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein -coupled receptors and comprise the largest gene superfamily in the mammalian genome.
PDZ domains have been established as sites for protein-protein interaction and play a central role in organizing diverse cell signaling assemblies. In the present study, we show that multi-PDZ domain protein 1 MUPP1 is expressed in the apical compartment of olfactory sensory neurons.
Furthermore, on heterologous co-expression with olfactory sensory neurons, MUPP1 was shown to translocate to the plasma membrane. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens - 1 distribution.
Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats.
In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated twice daily for 3 days treatment than single treatment before aspirin administration.
Immunostaining of zonula occludens ZO -1, one of the tight junctional proteins , was strengthened in rat gastric mucosa after repeated administration of rebamipide.
In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.
Human sperm degradation of zona pellucida proteins contributes to fertilization. The mammalian oocyte extracellular matrix known as the zona pellucida ZP acts as a barrier to accomplish sperm fusion with the female gamete. Although penetration of the ZP is a limiting event to achieve fertilization, this is one of the least comprehended stages of gamete interaction.
Even though previous studies suggest that proteases of sperm origin contribute to facilitate the passage of sperm through the ZP, in human this process is not yet fully understood. The aim of this study was to determine the ability of human sperm to degrade recombinant human ZP rhZPs proteins and to characterize the proteases involved in this process.
Purified rhZP2, rhZP3 and rhZP4 proteins were incubated with capacitated sperm and the proteolytic activity was determined by Western blot analysis. To further characterize the proteases involved, parallel incubations were performed in the presence of the protease inhibitors o-phenanthroline, benzamidine and MG meant to block the activity of metalloproteases, serine proteases and the proteasome, respectively.
Additionally, protease inhibitors effect on sperm-ZP binding was evaluated by hemizona assay. The results showed that rhZPs were hydrolyzed in the presence of capacitated sperm. O-phenanthroline inhibited the degradation of rhZP3, MG inhibited the degradation of rhZP4 and benzamidine inhibited the degradation of the three proteins under investigation. Moreover, hemizona assays demonstrated that sperm proteasome inhibition impairs sperm interaction with human native ZP.
This study suggests that sperm proteasomes could participate in the degradation of ZP, particularly of the ZP4 protein. Besides, metalloproteases may be involved in specific degradation of ZP3 while serine proteases may contribute to unspecific degradation of the ZP. These findings suggest that localized degradation of ZP proteins by sperm is probably involved in ZP penetration and may be of help in understanding the mechanisms of fertilization in humans.
Phosphorylation of zona occludens-2 by protein kinase C epsilon regulates its nuclear exportation. Here, we have analyzed the subcellular destiny of newly synthesized tight junction protein zona occludens ZO The mutation SA located within the nuclear exportation signal 1 of ZO-2 impairs the nuclear export of the protein. Our results strongly suggest that the departure of ZO-2 from the nucleus is regulated by phosphorylation at Ser by novel PKCepsilon.
To test the route taken by ZO-2 from synthesis to the plasma membrane, we devised a novel nuclear microinjection assay in which the nucleus served as a reservoir for anti-ZO-2 antibody. Through this assay, we demonstrate that a significant amount of newly synthesized ZO-2 goes into the nucleus and is later relocated to the plasma membrane.
These results constitute novel information for understanding the mechanisms that regulate the intracellular fate of ZO Aberrant expression of the tight junction molecules claudin-1 and zonula occludens - 1 mediates cell growth and invasion in oral squamous cell carcinoma.
We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction TJ molecules in oral carcinoma in situ CIS and squamous cell carcinoma SCC. To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 CLDN-1 and zonula occludens - 1 ZO-1 in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS.
ZO-1 was localized within the nucleus of proliferating cells. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion. All rights reserved. Rapidly evolving zona pellucida domain proteins are a major component of the vitelline envelope of abalone eggs.
Proteins harboring a zona pellucida ZP domain are prominent components of vertebrate egg coats. Although less well characterized, the egg coat of the non-vertebrate marine gastropod abalone Haliotis spp. Egg coat proteins from vertebrate as well as non-vertebrate taxa have been shown to evolve under positive selection. Studied most extensively in the abalone system, coevolution between adaptively diverging egg coat and sperm proteins may contribute to the rapid development of reproductive isolation.
Thus, identifying the pattern of evolution among egg coat proteins is important in understanding the role these genes may play in the speciation process. The purpose of the present study is to characterize the constituent proteins of the egg coat [vitelline envelope VE ] of abalone eggs and to provide preliminary evidence regarding how selection has acted on VE proteins during abalone evolution.
A proteomic approach is used to match tandem mass spectra of peptides from purified VE proteins with abalone ovary EST sequences, identifying 9 of 10 ZP domain proteins as components of the VE. Maximum likelihood models of codon evolution suggest positive selection has acted among a subset of amino acids for 6 of these genes. This work provides further evidence of the prominence of ZP proteins as constituents of the egg coat, as well as the prominent role of positive selection in diversification of these reproductive proteins.
Directory of Open Access Journals Sweden. Full Text Available Protein -carbohydrate interaction regulates multiple important processes during fertilization, an essential biological event where individual gametes undergo intercellular recognition to fuse and generate a zygote.
In the mammalian female reproductive tract, sperm temporarily adhere to the oviductal epithelium via the complementary interaction between carbohydrate-binding proteins on the sperm membrane and carbohydrates on the oviductal cells. After detachment from the oviductal epithelium at the appropriate time point following ovulation, sperm migrate and occasionally bind to the extracellular matrix, called the zona pellucida ZP, which surrounds the egg, thereafter undergoing the exocytotic acrosomal reaction to penetrate the envelope and to reach the egg plasma membrane.
This sperm-ZP interaction also involves the direct interaction between sperm carbohydrate-binding proteins and carbohydrates within the ZP, most of which have been conserved across divergent species from mammals to amphibians and echinoderms.
This review focuses on the carbohydrate-mediated interaction of sperm with the female reproductive tract, mainly the interaction between sperm and the ZP, and introduces the fertilization-suppressive action of dicalcin, a Xenopus laevis ZP protein -associated protein. The action of dicalcin correlates significantly with a dicalcin-dependent change in the lectin-staining pattern within the ZP, suggesting a unique role of dicalcin as an inherent protein that is capable of regulating the affinity between the lectin and oligosaccharides attached on its target glycoprotein.
Immune response in rabbit ovaries following infection of a recombinant myxoma virus expressing rabbit zona pellucida protein B. In this study, we investigated the autoimmune response in rabbit ovaries following infection with a recombinant myxoma virus expressing rabbit zona pellucida protein B MV-ZPB.
A specific IgG antibody response to ZPB was elicited in the serum of infected rabbits and the antibody strongly bound to the zona pellucida of oocytes in secondary and tertiary follicles. T cell infiltration in the ovary was detected in a small proportion of the infected rabbits. In spite of this, the mean number of preovulatory and tertiary follicles in the ovary was significantly reduced at 30 days postinfection compared with that of the infected and uninfected controls.
Histological analysis revealed that the cortex and medulla of these ovaries had accumulated a large number of probably luteinized cells and there were no follicles in these areas, indicating the ovaries were in a severe pathological condition.
The data suggest that the delivery of ZP antigens using a recombinant myxoma virus is a prospective way to develop immunocontraceptive vaccines for rabbit population control, but that more understanding of the kinetics of the autoimmune response induced by viral delivery is needed. Effects of exposure of epididymal boar spermatozoa to seminal plasma on the binding of zona pellucida proteins during in vitro capacitation.
The purpose of the investigation was to determine whether seminal plasma plays a role in the increase during in vitro capacitation of the number of boar spermatozoa with enhanced binding of zona pellucida proteins. Ejaculated spermatozoa and spermatozoa collected from the caudae epididymides of. With the aim of discovering new molecular interactions of the tight junction protein ZO-2, a two-hybrid screen was performed on a human kidney cDNA library using as bait the middle segment of ZO Nocodazole treatment and wash out reveals that ZASP disappears from the nucleus during mitosis in accordance with speckle disassembly during metaphase.
Involvement of adenosine monophosphate activated kinase in interleukin-6 regulation of steroidogenic acute regulatory protein and cholesterol side chain cleavage enzyme in the bovine zona fasciculata and zona reticularis. In bovine adrenal zona fasciculata ZF and NCI-HR cells, interleukin-6 IL-6 increases cortisol release, increases expression of steroidogenic acute regulatory protein StAR , cholesterol side chain cleavage enzyme Pscc , and steroidogenic factor 1 SF-1 increases steroidogenic proteins , and decreases the expression of adrenal hypoplasia congenita-like protein DAX-1 inhibits steroidogenic proteins.
Jimenez, B. Many different classes of environmental contaminants such as industrial chemicals e. Avian raptor species, such as peregrine falcon Falco peregrinus for their peculiar position in the food web are potentially at risk in relation to the accumulation of Persistent Organic Pollutants POPs and toxic metals. Thus there is a need to develop sensitive diagnostic monitoring tools for the evaluation of toxicological risk and potential effects on the reproductive function and population dynamic of avian top predator species.
Vtg, a complex phospholipoglycoprotein, is the major egg-yolk protein precursor and is normally synthesized by females in response to estradiol. These proteins Vtg, ZR and ZP are normally synthesised in the liver as a response to an estrogen signal given by Estradiol. Males and sexually undifferentiated specimens also have the Vtg and ZR genes but do not express them unless exposed to estrogenic compounds.
The main aim of this preliminary study was to develop methods for the detection of Vtg and ZR in plasma obtained from peregrine falcon as a specific biomarker for the evaluation of the effects of EDCs.
G protein -coupled receptors GPCRs contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases.
As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins , postsynaptic density protein of 95 kilodaltons, disc large, zona occludens - 1 PDZ domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms.
PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action.
Loss of the zona pellucida-binding protein 2 Zpbp2 gene in mice impacts airway hypersensitivity and lung lipid metabolism in a sex-dependent fashion. The human chromosomal region 17qq21 is one of the best replicated genome-wide association study loci for childhood asthma. The associated SNPs span a large genomic interval that includes several protein -coding genes.
Here, we tested the hypothesis that the zona pellucida-binding protein 2 ZPBP2 gene residing in this region contributes to asthma pathogenesis using a mouse model. We tested the lung phenotypes of knock-out KO mice that carry a deletion of the Zpbp2 gene. The deletion attenuated airway hypersensitivity AHR in female, but not male, mice in the absence of allergic sensitization.
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