Extracellular vesicle formation and release pathway (EV pathway)

The extracellular vesicle (EV) formation and release pathway is a fundamental cellular process involving the biogenesis and secretion of membrane-bound particles, primarily exosomes and microvesicles (Catalano & O'Driscoll, 2020). Exosomes are derived from the endocytic pathway, where intraluminal vesicles (ILVs) form within multivesicular bodies (MVBs) through the action of the Endosomal Sorting Complex Required for Transport (ESCRT) or ESCRT-independent mechanisms involving lipids like ceramide (Trajkovic et al., 2008). Microvesicles, conversely, result from the direct outward budding and fission of the plasma membrane, a process regulated by calcium-dependent enzymes and cytoskeletal rearrangement (Li et al., 2018). These vesicles facilitate intercellular communication by transferring bioactive molecules, such as proteins, mRNA, and microRNA, to recipient cells, thereby influencing physiological and pathological processes (Mashouri et al., 2019). In diseases like cancer, the pathway is often upregulated to promote pre-metastatic niche formation and therapeutic resistance, while in neurodegenerative disorders, it may contribute to the spread of toxic protein aggregates like tau or alpha-synuclein (Kalluri & LeBleu, 2020). Pharmacological modulation of this pathway, using inhibitors like GW4869 or amiloride, is an active area of research aimed at curbing disease progression (Essandoh et al., 2015).

Other names

Extracellular vesicle biogenesisExosome secretion pathwayMicrovesicle shedding pathwayEV secretionExosome biogenesis and release

Inhibition of neutral sphingomyelinase 2 (nSMase2) to block ceramide-dependent budding, inhibition of Rab GTPases (e.g., Rab27a/b) to prevent multivesicular body docking, modulation of the actin cytoskeleton to inhibit plasma membrane shedding, or blockade of the ESCRT machinery (Catalano & O'Driscoll, 2020; Essandoh et al., 2015).