TY - JOUR A1 - Jonscher, Ernst A1 - Flemming, Sven A1 - Schmitt, Marius A1 - Sabitzki, Ricarda A1 - Reichard, Nick A1 - Birnbaum, Jakob A1 - Bergmann, Bärbel A1 - Höhn, Katharina A1 - Spielmann, Tobias T1 - PfVPS45 Is Required for Host Cell Cytosol Uptake by Malaria Blood Stage Parasites JF - Cell host & microbe N2 - During development in human erythrocytes, the malaria parasite Plasmodium falciparum internalizes a large part of the cellular content of the host cell. The internalized cytosol, consisting largely of hemoglobin, is transported to the parasite’s food vacuole where it is degraded, providing nutrients and space for growth. This host cell cytosol uptake (HCCU) is crucial for parasite survival but the parasite proteins mediating this process remain obscure. Here, we identify P. falciparum VPS45 as an essential factor in HCCU. Conditional inactivation of PfVPS45 led to an accumulation of host cell cytosol-filled vesicles within the parasite and inhibited the delivery of hemoglobin to the parasite's digestive vacuole, resulting in arrested parasite growth. A proportion of these HCCU vesicle intermediates was positive for phosphatidylinositol 3-phosphate, suggesting endosomal characteristics. Thus PfVPS45 provides insight into the elusive machinery of the ingestion pathway in a parasite that contains an endolysosomal system heavily repurposed for protein secretion. Y1 - 2018 U6 - https://doi.org/10.1016/j.chom.2018.11.010 SN - 1931-3128 SN - 1934-6069 VL - 25 IS - 1 SP - 166 EP - 173 PB - Cell Press CY - Cambridge ER -