Extracellular vesicles secretion: involvement of tne Snarevamp7 and the gtpase Rab39a

Abstract

Secretion of extracellular vesicles (EVs) exerts fundamental roles in almost every tissue, in both physiological and pathological conditions. EVs emerge as important structures involved in cellular communication, particularly in cancer, autoimmunity, infectious diseases, and neurodegenerative disorders. These small membranous formations contain a vast amount of different molecules like nucleic acids, lipids, proteins, and sugars. Hence, EVs could be useful as novel biomarkers and therapies for the treatment of numerous pathologies. Understanding the role played by proteins involved in EVs exocytosis is crucial to control their burden. Rab proteins are the master controllers of vesicular transport. Our laboratory has demonstrated that Rab39a co-localizes with CD63 at multivesicular bodies (MVBs) and regulates the transport of these vesicles. The French laboratory has shown the role of VAMP7 protein in EVs fusion with the plasma membrane. In this collaborative study, we found that Rab39a co-localized with VAMP7 in small vesicles. Furthermore, these proteins modulated EVs secretion in HeLa cells. Interestingly, in VAMP7-knockout cells, the amount of EVs released to the extracellular medium significantly decreased; therefore, EVs cargoes, including molecules with important functions in the immune system, were retained within cells. We found that Galectin-1, a protein of the lectin family, is released through VAMP7-dependent exocytosis. Consequently, impairing VAMP7 function might distort communication and signal transmission among cells, overall affecting immune response.