scholarly journals Membrane Trafficking of Integral Cell Junction Proteins

2021 ◽  
Author(s):  
Arie Horowitz

Though membrane trafficking of cell junction proteins has been studied extensively for more than two decades, the accumulated knowledge remains fragmentary. The goal of this review is to synthesize the numerous and disparate observations on the membrane trafficking of the five major junction transmembrane proteins accumulated to date to comprehend the current state of the art, to highlight differences and similarities among the trafficking pathways, and to identify topics that are not fully understood. Clathrin-mediated endocytosis appears to be the main but not exclusive mode of internalization. Caveolin-mediated endocytosis and macropinocytosis are employed less frequently. PDZ-domain binding is the predominant mode of interaction between junction protein cytoplasmic tails and scaffold proteins. It is shared by claudins, the largest family of junction integral proteins, and by the three nectins. All five proteins are destined to either recycling via Rab4/Rab11 GTPases or to degradation. The sorting mechanisms that underlie the specificity of their endocytic pathways and determine their fates are not fully known. New data is presented to introduce an emerging role of junction-associated scaffold proteins in claudin membrane trafficking.

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Cristina Bertocchi ◽  
Megha Vaman Rao ◽  
Ronen Zaidel-Bar

Adherens junctions connect the actin cytoskeleton of neighboring cells through transmembrane cadherin receptors and a network of adaptor proteins. The interactions between these adaptors and cadherin as well as the activity of actin regulators localized to adherens junctions are tightly controlled to facilitate cell junction assembly or disassembly in response to changes in external or internal forces and/or signaling. Phosphorylation of tyrosine, serine, or threonine residues acts as a switch on the majority of adherens junction proteins, turning “on” or “off” their interactions with other proteins and/or their enzymatic activity. Here, we provide an overview of the kinases and phosphatases regulating phosphorylation of adherens junction proteins and bring examples of phosphorylation events leading to the assembly or disassembly of adherens junctions, highlighting the important role of phosphorylation switches in regulating their dynamics.


2010 ◽  
Vol 1 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Piyush Tripathi ◽  
Manorama Tripathi

ABSTRACT Testis and ovary serve an important role of producing male and female gametes. Their normal functioning is very important for the proper formation of sperm and ovum and thus has a critical role in the successful fertility outcome. Synchronized activity of various cells in the gonads is needed to provide favorable niche for the growth and development of the germ cells. Among various ways of cellular communication, intercellular communication is mediated by gap junctions, which provides open but selective exchange of ion and molecules of restricted size between two adjoining cells. The basic unit of gap junction is connexins. Their important role has been speculated in the maintenance of homeostasis, morphogenesis, cell differentiation, and growth control in higher organisms. The expression of gap junction proteins in reproductive tissues has drawn the attention and interest of researcher to investigate their role in the reproductive outcome. The reports about the correlation of gap junction protein expression pattern in infertility patients and in animal models have suggested their implication in fertility. Some of these gap junction proteins seem to have redundant functions, whereas some could be very critical in the normal fertility and could not be dispensable for the successful outcome of the reproduction.


2008 ◽  
Vol 82 (7) ◽  
pp. 3555-3560 ◽  
Author(s):  
Laurent Meertens ◽  
Claire Bertaux ◽  
Lisa Cukierman ◽  
Emmanuel Cormier ◽  
Dimitri Lavillette ◽  
...  

ABSTRACT Hepatitis C virus (HCV) is a major cause of liver disease in humans. The CD81 tetraspanin is necessary but not sufficient for HCV penetration into hepatocytes, and it was recently reported that the tight junction protein claudin-1 is a critical HCV entry cofactor. Here, we confirm the role of claudin-1 in HCV entry. In addition, we show that claudin-6 and claudin-9 expressed in CD81+ cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. Whereas claudin-1, -6, and -9 function equally well as entry cofactors in endothelial cells, claudin-1 is more efficient in hepatoma cells. This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors. Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis.


2009 ◽  
Vol 20 (19) ◽  
pp. 4225-4234 ◽  
Author(s):  
Elsa Regan-Klapisz ◽  
Vincent Krouwer ◽  
Miriam Langelaar-Makkinje ◽  
Laxman Nallan ◽  
Michael Gelb ◽  
...  

In endothelial cells specifically, cPLA2α translocates from the cytoplasm to the Golgi complex in response to cell confluence. Considering the link between confluence and cell–cell junction formation, and the emerging role of cPLA2α in intracellular trafficking, we tested whether Golgi-associated cPLA2α is involved in the trafficking of junction proteins. Here, we show that the redistribution of cPLA2α from the cytoplasm to the Golgi correlates with adherens junction maturation and occurs before tight junction formation. Disruption of adherens junctions using a blocking anti-VE-cadherin antibody reverses the association of cPLA2α with the Golgi. Silencing of cPLA2α and inhibition of cPLA2α enzymatic activity using various inhibitors result in the diminished presence of the transmembrane junction proteins VE-cadherin, occludin, and claudin-5 at cell–cell contacts, and in their accumulation at the Golgi. Altogether, our data support the idea that VE-cadherin triggers the relocation of cPLA2α to the Golgi and that in turn, Golgi-associated cPLA2α regulates the transport of transmembrane junction proteins through or from the Golgi, thereby controlling the integrity of endothelial cell–cell junctions.


Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 476 ◽  
Author(s):  
Joanna Gemel ◽  
John Kilkus ◽  
Glyn Dawson ◽  
Eric Beyer

Intercellular communication is accomplished by passage of ions and small molecules through gap junction channels in directly contacting cells or by secretion and response to transmitters, hormones and extracellular vesicles in cells that are distant from each other. Recent studies have suggested that there may be overlap of these processes; specifically, small extracellular vesicles may contain subunit gap junction proteins, connexins. We isolated and analyzed extracellular vesicles secreted by cultured microvascular endothelial cells. These vesicles had a diameter of ~120 nm. They contained four exosomal proteins (flotillin-1, CD63, CD81 and Alix) and the gap junction protein, connexin43. They did not contain an endoplasmic reticulum protein (Grp94) or an adherens junction protein (VE-cadherin). Secretion of vesicles was increased by treatment of the cells with staurosporine. Our data confirm that the gap junction protein, connexin43, can be secreted in vesicles with the properties of exosomes. Although the role of vesicular connexin is not clearly known, we speculate that it might participate in docking/fusion of the exosomes with the recipient cell, transmission of vesicular contents, or cellular signaling.


Author(s):  
Lei Lu ◽  
Jing Lu ◽  
Yueyue Yu ◽  
Erika Claud

Abstract Background Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature neonates. Possible therapeutic approaches are centered on promoting maturation of the gastrointestinal mucosal barrier. Studies have demonstrated that antenatal administration of corticosteroids can decrease NEC incidence and mortality. Methods Pregnant rat dams were administered dexamethasone 48 h prior to delivery. The pups were subjected to an experimental NEC-like injury protocol. Ileal tissues and sera were collected and evaluated for inflammatory cytokines, gut permeability and expressions and localizations of tight junction proteins, and surfactant protein-D by immunohistochemistry/immunofluorescent staining. Intestinal epithelial cells (IEC-6) were pretreated with SP-D to examine the effect of SP-D on tight junction protein expressions when challenged with platelet-activating factor and lipopolysaccharide to model proinflammatory insults. Results Antenatal dexamethasone reduced systemic inflammation, preserved intestinal barrier integrity, and stimulated SP-D expression on the intestinal mucosal surface in pups exposed to NEC-like injury. Pretreatment of SP-D blocked platelet-activating factor/lipopolysaccharide-induced tight junction disruption in IEC-6 cells in vitro. Conclusions Antenatal dexamethasone preserves the development of intestinal mucosal barrier integrity and reduces incidence and morbidity from an experimental NEC-like injury model. Dexamethasone upregulation of intestinal SP-D-protective effects on tight junction proteins. Impact Antenatal administration of dexamethasone can function in concert with intestinal surfactant protein-D to decrease systemic inflammatory responses, and protect intestinal barrier integrity in a neonatal rat model of NEC. A novel role of intestinal SP-D in preserving tight junction protein structures under inflammatory conditions. We describe the intestinal SP-D—an overlooked role of antenatal dexamethasone in neonatal NEC?


Author(s):  
Francesco Manfrevola ◽  
Guillaume Martinez ◽  
Charles Coutton ◽  
Domenico Rocco ◽  
Karine Reynaud ◽  
...  

Ankyrin proteins (ANKRD) are key mediators linking membrane and sub-membranous cytoskeletal proteins. Recent findings have highlighted a new role of ANKRD31 during spermatogenesis, elucidating its involvement in meiotic recombination and male germ cell progression. Following testicular differentiation, spermatozoa (SPZ) enter into the epididymis, where they undergo several biochemical and enzymatic changes. The epididymal epithelium is characterized by cell-to-cell junctions that are able to form the blood-epididymal barrier (BEB). This intricate epithelial structure provides the optimal microenvironment needed for epididymal sperm maturation. To date, no notions have been reported regarding a putative role of ANKRD31 in correct BEB formation. In our work, we generated an Ankrd31 knockout male mouse model (Ankrd31–/–) and characterized its reproductive phenotype. Ankrd31–/– mice were infertile and exhibited oligo-astheno-teratozoospermia (a low number of immotile SPZ with abnormal morphological features). In addition, a complete deregulation of BEB was found in Ankrd31–/–, due to cell-to-cell junction anomalies. In order to suggest that BEB deregulation may depend on Ankrd31 gene deletion, we showed the physical interaction among ANKRD31 and some epithelial junction proteins in wild-type (WT) epididymides. In conclusion, the current work shows a key role of ANKRD31 in the control of germ cell progression as well as sperm and epididymal integrity.


Author(s):  
Svitlana Ilkovych ◽  
◽  
Maryna Korol ◽  

The article considers the essence of blockchain technology and the possibility of its application in the banking sector. The current state of development and application of blockchain technologies in various industries is analyzed. The pros and cons of using blockchain technologies for the banking sector are identified. Emphasis is placed on the role of blockchain technologies in the further development of the banking sector. The most promising directions of development of this technology are considered. Particular attention is paid to examples of the use of blockchain technology by global banking institutions.


Author(s):  
I. V. Bukhtiyarov

The article presents the results of the analysis of health, working conditions and prevalence of adverse production factors, the structure of the detected occupational pathology in the working population of the Russian Federation. The article presents Statistical data on the dynamics of the share of workplaces of industrial enterprises that do not meet hygienic standards, occupational morbidity in 2015-2018 for the main groups of adverse factors of the production environment and the labor process. The indicators of occupational morbidity over the past 6 years in the context of the main types of economic activity, individual subjects of the Russian Federation, classes of working conditions, levels of specialized occupational health care. The role of the research Institute of occupational pathology and occupational pathology centers in solving organizational, methodological and practical tasks for the detection, treatment, rehabilitation and prevention of occupational diseases is shown. The basic directions of activity in the field of preservation and strengthening of health of workers, and also safety at a workplace are defined.


2020 ◽  
pp. 71-84
Author(s):  
Ярослав Очканов

Статья посвящена исследованию малоизученной стороны деятельности видного русского священнослужителя протоиерея Евгения Попова, бывшего с 1842 по 1875 гг. настоятелем русской посольской церкви в Лондоне. Его служение на Английской земле совпало с углублением диалога между Русской Православной и Англиканской церквами, явившегося следствием религиозных преобразований в Англии в 1830 - 1840-е гг. Отец Евгений в рассматриваемый период фактически стал связующим звеном между русским церковноначалием и англиканами - инициаторами единения двух Церквей. Он проделал огромную работу по популяризации православия в Англии и много сделал для ознакомления русской церковной общественности с вероучением и структурными особенностями англиканства. Материалом для исследования послужили, прежде всего, письма протоиерея Евгения Попова обер-прокурорам Святейшего Синода Н. А. Протасову и А. П. Толстому. Эти документы являются своеобразными отчётами о современном состоянии Англиканской Церкви, о религиозных течениях в ней и усилиях, предпринимаемых определёнными церковными кругами в Англии по сближению с православием. Результаты его деятельности имели важное значение в последующие десятилетия, когда англикано-православный диалог вышел на церковно-государственный уровень. The article is devoted to the insufficiently studied aspects of Russian prominent cleric Archpriest Eugene Popov, rector of Russian Embassy Church in London from 1842 to 1875. His Ministry on the English soil coincided with the deepening of the dialogue between the Russian Orthodox and Anglican Churches, which was the result of religious transformations in England in the 1830s and 1840s. Father Eugene in the period under consideration actually became a connecting link between the Russian Church authorities and the anglicans-initiators of the union of the two Churches. He had done a great job by popularizing Orthodoxy in England and by familiarizing the Russian Church community with the doctrine and structural features of Anglicanism. The study, first of all, is based the letters of Archpriest Yevgeny Popov to the chief prosecutors of the Holy Synod N. A. Protasov and A. P. Tolstoy, which were original reports on the current state of the Anglican Church, it’s religious trends, and the efforts made by certain Church circles in England to get closer to Orthodoxy. The fruits of his activities were important in the following decades, when the Anglican-Orthodox dialogue reached the Church-state level.


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