Fig. 3

Exosome biogenesis and cell–cell communication. ① Biogenesis of exosomes begins with inward budding of the plasma membrane to form an early endosome. ② A second inward budding of the early endosome generates a multivesicular body containing intraluminal vesicles. During the second inward budding, exosomes are loaded with their cargo (mRNAs, non-coding RNAs, proteins, and DNA fragments). Exosomal biogenesis can occur through both ESCRT-dependent and ESCRT-independent pathways. ③ and ④ The multivesicular body can fuse either to a lysosome for the degradation of its components or to the plasma membrane for secretion. ⑤ and ⑥ The multivesicular body ultimately fuses with the plasma membrane to release its intraluminal vesicles into the extracellular space as exosomes. The released exosomes may be taken up by target cells through ⑦ receptor-mediated endocytosis, ⑧ direct fusion with the recipient plasma membrane, ⑨ phagocytosis and macropinocytosis, or ⑩ caveolin- and clathrin-mediated endocytosis. ESCRT endosomal sorting complex required for transport