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The threat of emerging malaria strains resistant to currently available drugs has made the search for novel drug targets compelling. The process by which <jats:italic>Plasmodium falciparum<\/jats:italic> parasites invade the host cell has been widely studied, but only a few erythrocyte proteins involved in this process have been identified so far. The erythrocyte protein Rac1 is a GTPase that plays an important role in host cell invasion by many intracellular pathogens. Here we show that Rac1 is recruited in proximity to the site of parasite entry during <jats:italic>P. falciparum<\/jats:italic> invasion process and that subsequently localizes to the parasitophorous vacuole membrane. We also suggest that this GTPase may be involved in erythrocyte invasion by <jats:italic>P. falciparum<\/jats:italic>, by testing the effect of specific Rac1 inhibitory compounds. Finally, we suggest a secondary role of the erythrocyte GTPase also in parasite intracellular development. We here characterize a new erythrocyte protein potentially involved in <jats:italic>P. falciparum<\/jats:italic> invasion of the host cell and propose the human GTPase Rac1 as a novel and promising antimalarial drug target.<\/jats:p>","DOI":"10.1038\/s41598-020-79052-0","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T11:24:50Z","timestamp":1608117890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion"],"prefix":"10.1038","volume":"10","author":[{"given":"Silvio","family":"Paone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"D\u2019Alessandro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Parapini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Celani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Tirelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoochehr","family":"Pourshaban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Olivieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"79052_CR1","unstructured":"WHO. 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