Figure 1.

Models of Ral function in exosome biogenesis and secretion. (A) MVBs can either enter a degradation pathway by maturing into lysosomes or induce the secretion of the heterogenous populations of intraluminal vesicles (ILV) they contain by fusing with the plasma membrane and liberating exosomes in the extracellular space. (B) In total absence of the GTPase RAL-1 in C. elegans, the formation of ILVs is reduced and MVBs are enlarged (one extreme example of ral-1 phenotype is presented). Ral could orchestrate the inward budding of ILVs by controlling the localization or the activation of PLD, directly or via Arf6 activation, which in turn affects the local enrichment of the lipid Phosphatidic Acid (PA). PA induces negative membrane curvature and directly interacts with syntenin (Synt), which promotes ILV budding trough its interaction with Alix (Alx) and syndecan (Synd). (C) In addition, partial depletion of RAL-1 in C. elegans leads to an accumulation of MVBs docked to the plasma membrane. Ral could control the fusion between MVB and the plasma membrane, by promoting the localization of the t-SNARE Syntaxin 5 (Syx5), which would interact with an unknown v-SNARE present at the surface of the MVB to promote fusion and exosome release.