Endosomal signalling via exosome surface TGFβ-1

Shelke GV, Yin Y, Jang SC, Lässer C, Wennmalm S, Hoffmann HJ, Li L, Gho YS, Nilsson JA, Lötvall J

J Extracell Vesicles 8 (1) 1650458 [2019-12-01; online 2019-09-20]

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 β-1 (TGFβ-1) on their surfaces. The latent form of TGFβ-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 TGFβ-1 is retained within the endosomal compartments at the time of signalling, which results in prolonged cellular signalling compared to free-TGFβ-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 TGFβ-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.

Glycoproteomics and MS Proteomics [Service]

Integrated Microscopy Technologies Gothenburg [Service]

Integrated Microscopy Technologies Stockholm

PubMed 31595182

DOI 10.1080/20013078.2019.1650458

Crossref 10.1080/20013078.2019.1650458

Publications 9.5.0