Fig. 3.

Crosstalk between exosome biogenesis and autophagy. Link between exosome biogenesis and autophagy pathways exists not only at molecular level but also at membranous vesicles such as amphisomes. In this cooperative action, various Rab-GTPase proteins including Rab8a, Rab11, and Rab27 control the movement of vesicles between exosomal secretory pathway and autophagy at the cytoplasm. Autophagic proteins including LC3β, ATG5, and ATG16L1, on the MVB’s membrane, contribute to generate exosomes. Then the autophagic cargo can be secreted into extracellular milieu via exosomes. Additionally, the MVBs may fuse with autophagosome to make hybrid vesicles named amphisomes. Amphisomes cargo may be degraded by lysosomes or alternatively may fuse with the plasma membrane and secrete cargo into extracellular milieu. Amphisomes participate in packaging of annexin A2 (ANXA2) into exosomes; however, which cargo received from autophagosomes may sort into exosomes in amphisomes is still remains a mystery