Fig. 2

The exosome pathway. These small vesicles (30–120 nm) of endocytic origin are formed by inside budding of the membrane of late endosomes, generating multivesicular bodies (MVBs), and are released into the extracellular matrix by fusion of the MVBs with the plasma membrane (secretion pathway). Alternatively, MVBs may fuse with lysosomes for hydrolysis of exosomes (degradation pathway) or back-fuse with the plasma membrane for recycling such molecules (back-fusion pathway). Exosome cargo may consist of endocytosis, Golgi apparatus, and cytoplasm. Various molecules contribute to biogenesis of exosomes, including the ESCRT machinery, tetraspanins and lipids (ceramide). It is still unclear whether these mechanisms simultaneously generate the same MVB or not. Various Rab-GTPase proteins (Rab7, Rab11, Rab27a,-b, and Rab35) are involved in the intracellular trafficking of MVBs/exosome. Furthermore, SNAREs have been proposed to facilitate the fusion of MVBs with the plasma membrane. EE: early endosome; ER: endoplasmic reticulum; GA: Golgi apparatus; L: lysosome; N: nucleus