Figure 5.

Role of sphingomyelinases and ceramides in EV formation. Sphingomyelinases are active at the level of endosomes and cell membranes whereas their natural products, ceramides, are involved in the biogenesis and secretion of EVs. Neutral sphingomyelinase (nSMase) and ceramides participate in the endosomal formation of exosomes in an ESCRT-independent pathway. Acid sphingomyelinases (aSMase) targeted directly or indirectly via lysosomal exocytosis to the cell membrane contribute to creating ceramide-enriched microdomains that are involved in microvesicle and exosome formation and secretion.