Fig. 1

Mechanisms of exosome formation and secretion. During the initial invagination of the plasma membrane, various extracellular components, including surface proteins, are internalized as the membrane folds inward, resulting in the formation of ESEs. The GA and the ER play critical roles in producing and enabling the fusion of ESEs. During this process, the content carried by the ESEs is transferred, allowing them to mature into LSEs. In the subsequent stage, ILVs of varying sizes and contents form within LSEs through another invagination event, during which the cargo undergoes further modifications. LSEs are transformed into MVBs, which encapsulate ILVs earmarked for release as exosomes. When MVBs fuse with the plasma membrane, ILVs are released into the extracellular space via exocytosis, thereby becoming exosomes. Alternatively, MVBs may also fuse with autophagosomes or lysosomes for degradation and recycling within the cell. Exosomes are formed and released through either an endosomal sorting complex required for the transport (ESCRT)-dependent mechanism or a non-ESCRT-dependent mechanism, depending on the specific cargo and cell type involved. Several proteins serve as exosomal markers, including surface proteins such as CD9, CD63, and CD81, alongside cytoplasmic proteins such as flotillin, tumour susceptibility gene 101 (TSG101), apoptosis linked gene 2 interacting protein X (Alix), and the heat shock protein HSP70. Exosomes are rich in various types of biomolecular information. In contrast, microvesicles bud directly from the plasma membrane and are released into the extracellular space through an outward growth process