Figure 1.

Schematic diagram of cellular EVs, their surface molecules and their contents. The surface of EVs is decorated with different types of molecules that play important roles in their biogenesis, trafficking and function. These molecules include: (1) antigen-presenting molecules, such as major histocompatibility complex (MHC) class I and II, which are involved in immune recognition and modulation; (2) adhesion molecules, such as integrin-α and β, and P-selectin, which mediate EV binding and uptake by target cells; (3) signalling receptors, such as Fas ligand (FasL), tumor necrosis factor (TNF) receptor and transferrin receptor (TfR), which trigger intracellular signalling pathways upon EV interaction; (4) glycoproteins, such as N-linked glycans, O-linked glycans and beta-galactosidase, which modulate EV stability, solubility and bioactivity; (5) lipids, such as sphingomyelin, ceramides, cholesterol, phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and ganglioside GM1, which affect EV membrane fluidity, curvature and charge; and (6) tetraspanins, such as CD9, CD37, CD53, CD63, CD81 and CD82, which are the most abundant and characteristic proteins on EV surfaces and participate in EV formation, sorting and targeting. The contents of EVs are enriched with different types of molecules that reflect the origin and function of the EV. These molecules include: (1) heat shock proteins, such as HSP20, HSP27, HSP60, HSP90 and HSC70, which are involved in protein folding, stability and protection from stress; (2) cytokines and growth factors, such as tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) and TNF-related apoptosis-inducing ligand (TRAIL), which modulate immune responses, inflammation and cell survival; (3) cytoskeletal proteins, such as tubulin, actin and cofilin, which regulate EV shape, size and release; (4) membrane transport and fusion proteins, such as annexins, dynamin, syntaxin, Rabs, flotillin and GTPases, which facilitate EV budding, trafficking and fusion with target membranes; (5) endosomal sorting complex required for transport (ESCRT) machinery, such as tumor susceptibility gene 101 (TSG-101) and ALIX, which mediate EV formation and sorting of cargo molecules; (6) DNA, such as mitochondrial DNA (mtDNA), double-stranded DNA (dsDNA), single-stranded DNA (ssDNA) and viral DNA, which can transfer genetic information and induce immune responses; and (7) RNA, such as messenger RNA (mRNA), microRNA (miRNA), precursor miRNA (pre-miRNA), gamma-RNA (γ-RNA), circular RNA (circRNA), mitochondrial RNA (mtRNA), transfer RNA (tRNA), transfer strand RNA (tsRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA) and piwi-interacting RNA (piRNA), which can regulate gene expression and cellular functions in target cells. EVs extracellular vesicles