1. Orthologs of Plasmodium ICM1 are dispensable for Ca 2+ mobilization in Toxoplasma gondii .
- Author
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Cabral G, Ren B, Bisio H, Otey D, Soldati-Favre D, and Brown KM
- Subjects
- Animals, Humans, Mice, Plasmodium genetics, Plasmodium metabolism, Plasmodium falciparum genetics, Plasmodium falciparum metabolism, Toxoplasma genetics, Toxoplasma metabolism, Protozoan Proteins genetics, Protozoan Proteins metabolism, Calcium metabolism
- Abstract
Apicomplexan parasites mobilize ionic calcium (Ca
2+ ) from intracellular stores to promote microneme secretion and facilitate motile processes including gliding motility, invasion, and egress. Recently, a multipass transmembrane protein, ICM1, was found to be i mportant for c alcium m obilization in Plasmodium falciparum and P. berghei . Comparative genomics and phylogenetics have revealed putative ICM orthologs in Toxoplasma gondii and other apicomplexans. T. gondii possesses two ICM-like proteins, which we have named TgICM1-L (TGGT1_305470) and TgICM2-L (TGGT1_309910). TgICM1-L and TgICM2-L localized to undefined puncta within the parasite cytosol. TgICM1-L and TgICM2-L are individually dispensable in tachyzoites, suggesting a potential compensatory relationship between the two proteins may exist. Surprisingly, mutants lacking both TgICM1-L and TgICM2-L are fully viable, exhibiting no obvious defects in growth, microneme secretion, invasion, or egress. Furthermore, loss of TgICM1-L, TgICM2-L, or both does not impair the parasite's ability to mobilize Ca2+ . These findings suggest that additional proteins may participate in Ca2+ mobilization or import in Apicomplexa, reducing the dependence on ICM-like proteins in T. gondii . Collectively, these results highlight similar yet distinct mechanisms of Ca2+ mobilization between T. gondii and Plasmodium .IMPORTANCECa2+ signaling plays a crucial role in governing apicomplexan motility; yet, the mechanisms underlying Ca2+ mobilization from intracellular stores in these parasites remain unclear. In Plasmodium , the necessity of ICM1 for Ca2+ mobilization raises the question of whether this mechanism is conserved in other apicomplexans. Investigation into the orthologs of Plasmodium ICM1 in T. gondii revealed a differing requirement for ICM proteins between the two parasites. This study suggests that T. gondii employs ICM-independent mechanisms to regulate Ca2+ homeostasis and mobilization. Proteins involved in Ca2+ signaling in apicomplexans represent promising targets for therapeutic development., Competing Interests: The authors declare no conflict of interest.- Published
- 2024
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