Elucidation of the function of RON3 in the specific ion channel formation mechanism of erythrocyte stage Plasmodium

The emergence and spread of artemisinin-resistant Plasmodium falciparum is a serious problem in current malaria control. This study focused on parasitic membrane channels and erythrocyte membrane channels in erythroid stage malaria parasites as targets for the development of therapeutic agents that prevent the spread of artemisinin-resistant parasites and prevent the acquisition of new resistance, and are involved in both ion channel activities. First, RON3-DDD protozoa were used, which expresses RON3 protein with a DHFR-based destabilization domain (DDD) added to the C-terminus of Escherichia coli-derived dihydrofolate reductase, and investigated trimethoprim, which induces decreased channel activity. The effect of DDD destabilization in the absence of (TMP) on RON3 protein was verified by Western blotting. RON3 protein is processed into RON3N and RON3C in mitotic cells, and this processing was observed even in the absence of TMP. On the other hand, RON3N and RON3C signals decreased in the absence of TMP in cricoids. In addition, RON3N signals were observed in immunoprecipitates using RON3C as bait using ring bodies in the presence of TMP. This suggests that the formation of a complex between RON3N and RON3C is important for translocation of RON3 protein to the parasitic membrane of the ring, and that the presence or absence of this complex affects the formation of parasitic membrane channels.

Project details

Basic Science

Apr 2021 — Mar 2024

$36,840

Japan