外泌体 z-bo 2020-10-29 361

　　Exosomes exist in a variety of biological fluids, and through the proteins, nucleic acids, lipids and metabolites they carry, immune responses, viral infections, metabolism and cardiovascular diseases, neurodegenerative diseases and cancer progression progress between cells communication. Such as various physiological and pathological processes. When the endosome transforms into a mature multivesicular endosome (MVE), the endosome membrane germinates into the lumen, forming intraluminal vesicles (ILV). MVE fuses with the cell membrane and releases ILV outside the cell to form exosomes. Currently, the sprouting of the endosomal membrane forming ILV is thought to be mainly due to the transport of the necessary endosomal sorting complex (ESCRT), but in cells lacking ESCRT, the presence of ILV in MVE is observed and becomes ESCRT.

　　Recently, the Anti-Tiebang team of Sun Yat-sen University Cancer Center published a research paper on the independent exosomal pathway of RAB31marksandcontrolsan ESCRT in Cell Research. I deepened my understanding of exosomal biosynthesis. Before MVE fuses with the cell surface to secrete exosomes, an important checkpoint must be to prevent ILV degradation by preventing MVE-lysosome fusion. The accumulated non-degradable MVE uses a common exosomal secretion mechanism mainly regulated by RAB27. Therefore, the exosomal biosynthetic pathway involves three main steps involved in endosomal vesicle transport. The formation of ILV prevents the degradation of MVE and the fusion of MVE with the cell surface. Many membrane proteins have been detected in exosomes, which are involved in immune response, viral infection, metabolism, cardiovascular disease, neurodegenerative diseases and cancer progression, but their regulatory mechanism is still a mystery. This study found that active RAB31 drives EGFR to MVE to form ILV and exosomes, while EGFR and other possible RTKs phosphorylate RAB31 to drive exosomes formation. The Flotillin protein in the lipid raft domain is involved in the formation of this ILV driven by active RAB31, which has nothing to do with the ESCRT mechanism. It further proved that RAB31 mobilized TBC1D2B to inactivate RAB7, inhibit the fusion of MVE and lysosomes, and secrete exosomes. These findings establish an ESCRT-independent exosomal pathway marked and regulated by RAB31, and provide a bright spot for a better understanding of exosomal biosynthesis.