Orthologs of ICM1 Are Dispensable for Ca Mobilization in

Overview

Journal Microbiol Spectr

Specialty Microbiology

Date 2024 Aug 20

PMID 39162502

Authors

Gabriel Cabral

Bingjian Ren

Hugo Bisio

Dawson Otey

Dominique Soldati-Favre

Kevin M Brown

Affiliations

Soon will be listed here.

Abstract

Apicomplexan parasites mobilize ionic calcium (Ca) 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 mportant for alcium obilization in and . Comparative genomics and phylogenetics have revealed putative ICM orthologs in and other apicomplexans. 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. These findings suggest that additional proteins may participate in Ca mobilization or import in Apicomplexa, reducing the dependence on ICM-like proteins in . Collectively, these results highlight similar yet distinct mechanisms of Ca mobilization between and .IMPORTANCECa signaling plays a crucial role in governing apicomplexan motility; yet, the mechanisms underlying Ca mobilization from intracellular stores in these parasites remain unclear. In , the necessity of ICM1 for Ca mobilization raises the question of whether this mechanism is conserved in other apicomplexans. Investigation into the orthologs of ICM1 in revealed a differing requirement for ICM proteins between the two parasites. This study suggests that employs ICM-independent mechanisms to regulate Ca homeostasis and mobilization. Proteins involved in Ca signaling in apicomplexans represent promising targets for therapeutic development.

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