fig2

Figure 2. Cytoskeletal regulation of the exosome lifecycle. Schematic of the four stages of the exosome lifecycle - biogenesis, intracellular transport, release, and uptake by recipient cells - and their regulation by the cytoskeleton under mechanical stress. (A) Biogenesis. ER/TGN supply membrane and cargo to ESEs. ESEs mature into LSEs, which generate MVBs via second invagination. Rho GTPases drive actin-mediated membrane invagination; (B) Intracellular transport. MVBs are transported along microtubules toward lysosomes for degradation or toward the plasma membrane for secretion; (C) Release. MVBs fuse with the plasma membrane via SNARE complexes, releasing exosomes carrying resistance-associated cargo; (D) Uptake. Exosomes are internalized by target cells via phagocytic cup formation and transported along microtubules to ER/mitochondria, conferring a drug-resistant phenotype. ER: Endoplasmic reticulum; TGN: trans-Golgi network; ESEs: early-stage sorting endosomes; LSEs: late-stage sorting endosomes; MVBs: multivesicular bodies; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor.