A novel exosome biogenesis mechanism: multivesicular structures budding and rupturing at the plasma membrane

Exosomes are small vesicles secreted by the cells, which mediate intercellular signalling and systemic physiological processes. Exosomes are known to originate from the intraluminal vesicles of the multivesicular endosome that fuses with the plasma membrane. We found that the non-small cell lung cancer (NSCLC) cell lines, HCC15 and A549, secreted exosomes with typical morphology and protein contents. Unexpectedly, transmission electron microscopy images indicated that the cells formed multivesicular structures that protruded from the plasma membrane and ruptured to release the exosomes. There were smooth multivesicular structures surrounded by an ordinary looking membrane, multivesicular structures coated by an electron dense layer with regular spacing pattern, and intermediate forms that combined elements of both. Electron microscopy images suggested that exosomes are release from these structures by burst events and not by the conventional fusion process. The molecular details of this novel mechanism for membrane association, deformation and fusion is to be unveiled in the future.