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

Author:

Soares Ana Rosa,Martins-Marques Tania,Ribeiro-Rodrigues Teresa,Ferreira Joao Vasco,Catarino Steve,Pinho Maria João,Zuzarte Monica,Isabel Anjo Sandra,Manadas Bruno,P.G. Sluijter Joost,Pereira Paulo,Girao Henrique

Abstract

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.

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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