VAMP-associated protein-A and oxysterol-binding protein-related protein 3 promote the entry of late endosomes into the nucleoplasmic reticulum.
J Biol Chem
; 293(36): 13834-13848, 2018 09 07.
Article
in En
| MEDLINE
| ID: mdl-30018135
ABSTRACT
The endocytic pathway plays an instrumental role in recycling internalized molecules back to the plasma membrane or in directing them to lysosomes for degradation. We recently reported a new role of endosomes-the delivery of components from extracellular vesicles (EVs) to the nucleoplasm of recipient cells. Using indirect immunofluorescence, FRET, immunoisolation techniques, and RNAi, we report here a tripartite protein complex (referred to as the VOR complex) that is essential for the nuclear transfer of EV-derived components by orchestrating the specific localization of late endosomes into nucleoplasmic reticulum. We found that the VOR complex contains the endoplasmic reticulum-localized vesicle-associated membrane protein (VAMP)-associated protein A (VAP-A), the cytoplasmic oxysterol-binding protein-related protein 3 (ORP3), and late endosome-associated small GTPase Rab7. The silencing of VAP-A or ORP3 abrogated the association of Rab7-positive late endosomes with nuclear envelope invaginations and, hence, the transport of endocytosed EV-derived components to the nucleoplasm of recipient cells. We conclude that the VOR complex can be targeted to inhibit EV-mediated intercellular communication, which can have therapeutic potential for managing cancer in which the release of EVs is dysregulated.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endosomes
/
Carrier Proteins
/
Vesicular Transport Proteins
/
Multiprotein Complexes
/
Endoplasmic Reticulum
/
Nuclear Envelope
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2018
Document type:
Article