PT  - JOURNAL ARTICLE
AU  - Avalos-Padilla, Yunuen
AU  - Georgiev, Vasil N.
AU  - Lantero, Elena
AU  - Pujals, Silvia
AU  - Verhoef, René
AU  - Borgheti-Cardoso, Livia N.
AU  - Albertazzi, Lorenzo
AU  - Dimova, Rumiana
AU  - Fernàndez-Busquets, Xavier
TI  - The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during <em>Plasmodium falciparum</em> infection
AID  - 10.1101/2020.11.24.395756
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.24.395756
4099  - http://biorxiv.org/content/early/2020/11/24/2020.11.24.395756.short
4100  - http://biorxiv.org/content/early/2020/11/24/2020.11.24.395756.full
AB  - Infection with Plasmodium falciparum enhances extracellular vesicles (EVs) production in parasitized red blood cells (pRBC), an important mechanism for parasite-to-parasite communication during the asexual intraerythrocytic life cycle. The endosomal sorting complex required for transport (ESCRT), and in particular the ESCRT-III sub-complex, participates in the formation of EVs in higher eukaryotes. However, RBCs have lost the majority of their organelles through the maturation process, including an important reduction in their vesicular network. Therefore, the mechanism of EV production in P. falciparum-infected RBCs remains to be elucidated. Here we demonstrate that P. falciparum possesses a functional ESCRT-III machinery that is activated by an alternative recruitment pathway involving the action of PfBro1 and PfVps32/PfVps60 proteins. Additionally, multivesicular bodies formation and membrane shedding, both reported mechanisms of EVs production, were reconstituted in the membrane model of giant unilamellar vesicles using the purified recombinant proteins. Moreover, the presence of PfVps32, PfVps60 and PfBro1 in EVs purified from a pRBC culture was confirmed by super-resolution microscopy. In accordance, disruption of the Pfvps60 gene led to a reduction in the number of the produced EVs in the KO strain when compared with the parental 3D7 strain. Overall, our results increase the knowledge on the underlying molecular mechanisms during malaria pathogenesis and demonstrate that ESCRT-III P. falciparum proteins participate in EVs production.Competing Interest StatementThe authors have declared no competing interest.