Gap junctional protein Cx43 is involved in the communication between extracellular vesicles and mammalian cells.
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.
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Ana Rosa
AR
Soares
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Tania
T
Martins-Marques
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Teresa
T
Ribeiro-Rodrigues
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Joao Vasco
JV
Ferreira
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Steve
S
Catarino
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Maria João
MJ
Pinho
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Monica
M
Zuzarte
1] CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal [2] Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3004-517 Coimbra, Portugal.
Sandra
S
Isabel Anjo
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
Bruno
B
Manadas
1] Department of Cardiology, Division of Heart &Lungs, University Medical Center Utrecht, the Netherlands [2] Interuniversity Cardiology Institute Netherlands (ICIN), Utrecht, the Netherlands.
Joost
J
P G Sluijter
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Paulo
P
Pereira
Centre of Ophthalmology and Vision Sciences, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Sta Comba, 3000-354 Coimbra, Portugal.
Henrique
H
Girao
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D013058:Mass Spectrometry; D017208:Rats, Wistar
D018031:Connexin 43; C580592:Gja1 protein, rat; D004247:DNA