ESCRTindependent

ESCRT-independent refers to pathways of membrane vesicle formation and scission that do not involve the endosomal sorting complexes required for transport (ESCRT). In cellular biology, vesicles such as exosomes and microvesicles can be produced through ESCRT-dependent or ESCRT-independent mechanisms. The term is used to describe processes that occur without reliance on core ESCRT components.

Mechanisms described as ESCRT-independent often rely on membrane lipids and protein organizers to drive curvature and budding. Ceramide generation by neutral sphingomyelinases, particularly nSMase2, can promote inward budding of endosomal membranes and the formation of intraluminal vesicles within multivesicular bodies. Lipid-driven mechanisms may operate alongside or instead of ESCRT components. Tetraspanin-enriched microdomains, involving proteins such as CD9, CD63, and CD81, are also implicated in organizing cargo and facilitating vesicle budding in an ESCRT-independent manner. Cytoskeletal remodeling at the plasma membrane can further support microvesicle formation without ESCRT participation.

Evidence for ESCRT-independent pathways includes observations of vesicle production that persists when ESCRT components are reduced or absent, with cargo selection and vesicle characteristics influenced by lipid composition and tetraspanin organization. However, the relative contributions of ESCRT-dependent versus ESCRT-independent routes can vary by cell type and physiological context, and there is ongoing research to delineate when each pathway predominates.

Significance lies in understanding the full spectrum of vesicle biogenesis, with implications for intercellular communication, disease mechanisms, and strategies for exosome-based therapeutics and drug delivery.