Host PI(3,5)P2Activity Is Required forPlasmodium bergheiGrowth During Liver Stage Infection
| Autor: | Cristiana F. Pires, Mafalda Lopes da Silva, Laura Cabrita-Santos, Assia Shisheva, Miguel C. Seabra, Ognian C. Ikonomov, Elsa Seixas, Duarte C. Barral, José S. Ramalho, Carolina Thieleke-Matos |
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| Rok vydání: | 2014 |
| Předmět: |
Plasmodium berghei
Endosome Endocytic cycle Biochemistry Parasite load Parasite Load Article Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound PIKFYVE Transient Receptor Potential Channels Phosphatidylinositol Phosphates Structural Biology Cell Line Tumor parasitic diseases Genetics Animals Parasite hosting Phosphatidylinositol Molecular Biology Phosphoinositide-3 Kinase Inhibitors biology Cell Biology biology.organism_classification Endocytosis Cell biology Protein Transport Endocytic vesicle Liver chemistry |
| Zdroj: | Traffic. 15:1066-1082 |
| ISSN: | 1398-9219 |
| DOI: | 10.1111/tra.12190 |
| Popis: | 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), which converts phosphatidylinositol 3-phosphate [PI(3)P] into phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] in the endosomal system. We found that inhibition of PIKfyve either by pharmacological or non-pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P2 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)P2-dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection. |
| Databáze: | OpenAIRE |
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