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Endosomal signalling via exosome surface TGF beta-1

Journal article
Authors Ganesh V Shelke
Yanan Yin
Su Chul Jang
Cecilia Lässer
S. Wennmalm
H. J. Hoffmann
L. Li
Y. S. Gho
Jonas Andreas Nilsson
Jan Lötvall
Published in Journal of Extracellular Vesicles
Volume 8
Issue 1
Publication year 2019
Published at Institute of Clinical Sciences, Department of Surgery
Krefting Research Centre
Language en
Links dx.doi.org/10.1080/20013078.2019.16...
Keywords Mast cells, extracellular vesicles, exosomes, mesenchymal stem cells, tumour growth factor beta-1, cellular localization, endosomal signalling, proteoglycan, mesenchymal stem-cells, heparan-sulfate proteoglycans, growth-factor-beta, tgf-beta, mediated transfer, cancer exosomes, internalization, fibroblast, phenotype, migration, Cell Biology, ipale j, 1994, journal of cell biology, v124, p171
Subject categories Cell biology

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

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