scholarly journals Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes

2020 ◽  
Vol 3 (12) ◽  
pp. e202000821
Author(s):  
Tania Martins-Marques ◽  
Teresa Ribeiro-Rodrigues ◽  
Saskia C de Jager ◽  
Monica Zuzarte ◽  
Cátia Ferreira ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Extracellular Vesicle ◽  
Therapeutic Strategies ◽  
Target Cells ◽  
Comprehensive Strategy ◽  
Junction Protein ◽  
Gap Junction Protein

Ischemic heart disease has been associated with an impairment on intercellular communication mediated by both gap junctions and extracellular vesicles. We have previously shown that connexin 43 (Cx43), the main ventricular gap junction protein, assembles into channels at the extracellular vesicle surface, mediating the release of vesicle content into target cells. Here, using a comprehensive strategy that included cell-based approaches, animal models and human patients, we demonstrate that myocardial ischemia impairs the secretion of Cx43 into circulating, intracardiac and cardiomyocyte-derived vesicles. In addition, we show that ubiquitin signals Cx43 release in basal conditions but appears to be dispensable during ischemia, suggesting an interplay between ischemia-induced Cx43 degradation and secretion. Overall, this study constitutes a step forward for the characterization of the signals and molecular players underlying vesicle protein sorting, with strong implications on long-range intercellular communication, paving the way towards the development of innovative diagnostic and therapeutic strategies for cardiovascular disorders.

scholarly journals Gap junctional protein Cx43 is involved in the communication between extracellular vesicles and mammalian cells

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Ana Rosa Soares ◽  
Tania Martins-Marques ◽  
Teresa Ribeiro-Rodrigues ◽  
Joao Vasco Ferreira ◽  
Steve Catarino ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Mammalian Cells ◽  
Connexin 43 ◽  
Biological Effects ◽  
Biological Information ◽  
Target Cells ◽  
New Paradigm ◽  
Donor And Acceptor ◽  
Messenger Molecules

Abstract Intercellular communication is vital to ensure tissue and organism homeostasis and can occur directly, between neighbour cells via gap junctions (GJ), or indirectly, at longer distances, through extracellular vesicles, including exosomes. Exosomes, as intercellular carriers of messenger molecules, mediate the transfer of biological information between donor and acceptor cells. Although the biological effects of exosomes in target cells have been intensively studied, the mechanisms that govern exosomal uptake are not fully understood. Here, we show that Connexin 43 (Cx43), the most widely expressed GJ protein, is present in exosomes in the form of hexameric channels and, more importantly, that exosomal Cx43 is able to modulate the interaction and transfer of information between exosomes and acceptor cells. This study envisions a new paradigm where Cx43-containing channels mediate the release of exosomal content into cells, which constitutes a novel and unanticipated mechanism to modulate intercellular communication.

scholarly journals Navigating the Landscape of Tumor Extracellular Vesicle Heterogeneity

2019 ◽  
Vol 20 (6) ◽  
pp. 1349 ◽  
Author(s):  
Sabrina Roy ◽  
Hsing-Ying Lin ◽  
Chung-Yu Chou ◽  
Chen-Han Huang ◽  
Julia Small ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Extracellular Vesicle ◽  
Rapid Expansion ◽  
Parent Cell ◽  
Membrane Composition ◽  
Pathological Conditions ◽  
Respective Parent ◽  
Experimental Level

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level. Because of their relatively small size, EVs are difficult to reliably isolate and detect within a given sample. Consequently, standardized protocols that have been optimized for accurate characterization of EVs are lacking despite recent advancements in the field. Continuous improvements in pre-analytical parameters permit more efficient assessment of EVs, however, methods to more objectively distinguish EVs from background, and to interpret multiple single-EV parameters are lacking. Here, we review EV heterogeneity according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. In doing so, we also provide an overview of currently available and potentially applicable methods for single EV analysis. Finally, we examine the latest findings from experiments that have analyzed the issue at the single EV level and discuss potential implications.

scholarly journals Characterization of the Mitogen-activated Protein Kinase Phosphorylation Sites on the Connexin-43 Gap Junction Protein

1996 ◽  
Vol 271 (7) ◽  
pp. 3779-3786 ◽  
Author(s):  
Bonnie J. Warn-Cramer ◽  
Paul D. Lampe ◽  
Wendy E. Kurata ◽  
Martha Y. Kanemitsu ◽  
Lenora W. M. Loo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gap Junction ◽  
Connexin 43 ◽  
Mitogen Activated Protein Kinase ◽  
Phosphorylation Sites ◽  
Junction Protein ◽  
Mitogen Activated Protein ◽  
Gap Junction Protein ◽  
Kinase Phosphorylation

Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium

1999 ◽  
Vol 276 (2) ◽  
pp. H709-H717 ◽  
Author(s):  
Kevin Petrecca ◽  
Roxana Atanasiu ◽  
Sergio Grinstein ◽  
John Orlowski ◽  
Alvin Shrier
Keyword(s):  
Connexin 43 ◽  
Cell Types ◽  
Ph Homeostasis ◽  
Adult Rat ◽  
Junction Protein ◽  
Close Proximity ◽  
Gap Junction Protein ◽  
Intercalated Disks ◽  
Distinct Distribution ◽  
Intercalated Disk

The Na+/H+exchanger NHE1 isoform is an integral component of cardiac intracellular pH homeostasis that is critically important for myocardial contractility. To gain further insight into its physiological significance, we determined its cellular distribution in adult rat heart by using immunohistochemistry and confocal microscopy. NHE1 was localized predominantly at the intercalated disk regions in close proximity to the gap junction protein connexin 43 of atrial and ventricular muscle cells. Significant labeling of NHE1 was also observed along the transverse tubular systems, but not the lateral sarcolemmal membranes, of both cell types. In contrast, the Na+-K+-ATPase α1-subunit was readily labeled by a specific mouse monoclonal antibody (McK1) along the entire ventricular sarcolemma and intercalated disks and, to a lesser extent, in the transverse tubules. These results indicate that NHE1 has a distinct distribution in heart and may fulfill specialized roles by selectively regulating the pH microenvironment of pH-sensitive proteins at the intercalated disks (e.g., connexin 43) and near the cytosolic surface of sarcoplasmic reticulum cisternae (e.g., ryanodine receptor), thereby influencing impulse conduction and excitation-contraction coupling.

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