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

2015; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/srep13243

2045-2322

Ana da Rosa Soares, Tânia Martins‐Marques, Teresa Ribeiro‐Rodrigues, João Vasco Ferreira, Steve Catarino, Maria João Pinho, Mónica Zuzarte, Sandra I. Anjo, Bruno Manadas, Joost P. G. Sluijter, Paulo Pereira, Henrique Girão,

Photoacoustic and Ultrasonic Imaging

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.