Figure 8.

Model summarizing the VOR complex players and their interactions within NEI. A, presence of Rab7⁺ late endosomes (LE) in NEI requires VAP-A and ORP3, whereas ORP3 needs VAP-A, which is constitutively associated with ONM of type II NEI. B, VOR complex proteins (VAP-A, ORP3, Rab7) allow the tether of late endosomes to ONM in NEI (I). In this model, EVs are transported to late endosomes after their endocytosis. The lack of NEI-associated late endosomes and the inhibition of transfer of EV-derived components (soluble and membranous) into the nucleoplasm of host cells after importazole treatment (15) suggest that nuclear pores and importin β1 play a role in these processes (II). Their potential interaction (green question mark) with VOR complex and/or late endosomes should also be addressed. Other urgent questions remain open, notably the mechanism(s) allowing the extraction of EV-derived membrane proteins (green) from endosomal membrane (red) and their transfer into nucleoplasm through the nuclear pores, which are size-restricted (III, black question marks). EV, extracellular vesicle; LE, late endosome; INM, ONM, inner and outer nuclear membrane, respectively.