Elucidation of the mechanism of malaria parasite erythrocyte invasion controlled by DGK

Plasmodium malaria is an erythrocyte parasite that regulates the secretion of protozoan proteins through intracellular signaling when it invades the host erythrocyte. DGK1-deficient Plasmodium yoelii, one of the diacylglycerol kinases (DGK) that converts diacylglycerol (DAG) possessed by Plasmodium yoelii to phosphatidic acid (PA), is localized in cells of erythrocyte invasion-related molecules. The phenotype was shown to be a change in malaria, a decrease in molecular secretion, and the consequent decrease in the infection rate and pathogenicity of the protozoan to mice. Plasmodium bergina has two DGKs, and a DGK1 / DGK3 double-deficient protozoan was created to examine whether the two have complementary functions. Since there was no change in erythrocyte invasion efficiency between DGK1-deficient protozoans and DGK1 / DGK3 double-deficient protozoans, DGK1 is the only enzyme required for erythrocyte invasion of Plasmodium malaria and has a complementary effect between the two DGKs during the erythrocyte invasion process. I came to the conclusion that there is no. In addition, PA converted by DGK1 is known to bind to proteins having a PH domain, and the production and analysis of PH domain-induced deficient protozoans carried by protozoans were carried out in parallel. As a result, it was found that protozoans deficient in APH, which is one of the molecules having a PH domain, inhibit the surface secretion of erythrocyte invasion-related molecules in the same manner as DGK1-deficient protozoans. On the other hand, in APH-deficient protozoans, no change in intracellular localization of erythrocyte invasion-related molecules was observed. These results suggest that the interaction between PA and APH converted by DGK1 is essential for the secretion of erythrocyte invasion-related molecules, but the intracellular localization of these molecules may involve only DGK1-derived PA.

Project details

Basic Science

Sep 2020 — Mar 2021

$26,456

Japan