Premium
Host PI(3,5)P 2 Activity Is Required for Plasmodium berghei Growth During Liver Stage Infection
Author(s) -
ThielekeMatos Carolina,
da Silva Mafalda Lopes,
CabritaSantos Laura,
Pires Cristiana F.,
Ramalho José S.,
Ikonomov Ognian,
Seixas Elsa,
Shisheva Assia,
Seabra Miguel C.,
Barral Duarte C.
Publication year - 2014
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12190
Subject(s) - biology , microbiology and biotechnology , endocytic cycle , phosphatidylinositol , plasmodium berghei , endosome , plasmodium (life cycle) , parasite hosting , effector , vacuole , endocytosis , kinase , cell , immunology , malaria , biochemistry , cytoplasm , computer science , intracellular , world wide web
Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the Plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5‐kinase (PIKfyve) that converts phosphatidylinositol 3‐phosphate [PI(3)P] into phosphatidylinositol 3,5‐bisphosphate [PI(3,5)P 2 ] in the endosomal system. We found that inhibition of PIKfyve by either pharmacological or non‐pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P 2 effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3,5)P 2 ‐dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.