Exosomes: looking back three decades and into the future

Abstract

Exosomes are extracellular membrane vesicles whose biogenesis by exocytosis of multivesicular endosomes was discovered in 1983. Since their discovery 30 years ago, it has become clear that exosomes contribute to many aspects of physiology and disease, including intercellular communication. We discuss the initial experiments that led to the discovery of exosomes and highlight some of the exciting current directions in the field.

Figure 1.

Exocytosis of MVEs releases exosomes containing transferrin receptor. (left) View of an MVE from a fixed reticulocyte sparsely labeled with AuTf. The apparent fusion of the MVE and the plasma membrane may represent incipient MVE exocytosis. Bar, 100 nm. (right) View of MVE exocytosis in a reticulocyte labeled with AuTf, quick frozen without prior fixation, and freeze substituted. Bar, 200 nm. Figure and legend adapted from Harding et al. (1983).

Figure 2.

Model for routes of transferrin processing in reticulocytes (circa 1983–1984). Transferrin receptors (Tf-R) may recycle or be selectively shed from reticulocytes by trafficking in the following steps. (a) Diferric transferrin binds surface receptors, and receptor–ligand complexes are internalized via coated pits and vesicles. (b) Coat loss and fusion events produce a pleiomorphic class of small, uncoated vesicles and tubules. (c) Iron is removed from transferrin in an acid luminal environment and is transferred into the cytoplasm. (d) Apotransferrin remains bound to its receptor at acid pH, and both receptor and ligand recycle to the plasma membrane, where apotransferrin dissociates from the receptor. Alternatively, transferrin receptors destined to be shed from the cell segregate on inclusion vesicles of MVEs and are released by MVE exocytosis. Model and legend are adapted from Harding et al. (1984) and a precursor model in Harding et al. (1983).