Fig. 1. Exosome biogenesis pathways.

Exosomes are intracellularly generated inside MVBs. Endocytosis of the plasma membrane starts with endosome maturation, in which the limited membrane is invaginated to form ILVs. If ILVs are secreted outside the cells, they are called exosomes. Membrane protein clustering is an important mechanism by which membrane budding occurs. Syndecan clustering, tetraspanin enrichment, and high-molecular-weight multimer adiponectin-induced T-cadherin clustering are all supposed to enhance ILV biogenesis. Ceramide generation may affect membrane protein clustering in the late endosome and thereby induce ILV biogenesis. ER, endoplasmic reticulum.