Orthologs of Plasmodium ICM1 are dispensable for Ca 2+ mobilization in Toxoplasma gondii .

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 Ca ²⁺ . These findings suggest that additional proteins may participate in Ca ²⁺ mobilization or import in Apicomplexa, reducing the dependence on ICM-like proteins in T. gondii . Collectively, these results highlight similar yet distinct mechanisms of Ca ²⁺ mobilization between T. gondii and Plasmodium .IMPORTANCECa ²⁺ signaling plays a crucial role in governing apicomplexan motility; yet, the mechanisms underlying Ca ²⁺ mobilization from intracellular stores in these parasites remain unclear. In Plasmodium , the necessity of ICM1 for Ca ²⁺ 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 Ca ²⁺ homeostasis and mobilization. Proteins involved in Ca ²⁺ signaling in apicomplexans represent promising targets for therapeutic development.
Competing Interests: The authors declare no conflict of interest.