Endosomal signalling via exosome surface TGF?-1.

ABSTRACT: Extracellular vesicles such as exosomes convey biological messages between cells, either by surface-to-surface interaction or by shuttling of bioactive molecules to a recipient cell's cytoplasm. Here we show that exosomes released by mast cells harbour both active and latent transforming growth factor ?-1 (TGF?-1) on their surfaces. The latent form of TGF?-1 is associated with the exosomes via heparinase-II and pH-sensitive elements. These vesicles traffic to the endocytic compartment of recipient human mesenchymal stem cells (MSCs) within 60 min of exposure. Further, the exosomes-associated TGF?-1 is retained within the endosomal compartments at the time of signalling, which results in prolonged cellular signalling compared to free-TGF?-1. These exosomes induce a migratory phenotype in primary MSCs involving SMAD-dependent pathways. Our results show that mast cell-derived exosomes are decorated with latent TGF?-1 and are retained in recipient MSC endosomes, influencing recipient cell migratory phenotype. We conclude that exosomes can convey signalling within endosomes by delivering bioactive surface ligands to this intracellular compartment.

SUBMITTER: Shelke GV 

PROVIDER: S-EPMC6764367 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature