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Centrin2 from the human parasite Toxoplasma gondii is required for its invasion and intracellular replication.

ABSTRACT: Centrins are EF-hand containing proteins ubiquitously found in eukaryotes and are key components of centrioles/basal bodies as well as certain contractile fibers. We previously identified three centrins in the human parasite Toxoplasma gondii, all of which localized to the centrioles. However, one of them, T. gondii (Tg) Centrin2 (CEN2), is also targeted to structures at the apical and basal ends of the parasite, as well as to annuli at the base of the apical cap of the membrane cortex. The role(s) that CEN2 play in these locations were unknown. Here, we report the functional characterization of CEN2 using a conditional knockdown method that combines transcriptional and protein stability control. The knockdown resulted in an ordered loss of CEN2 from its four compartments, due to differences in incorporation kinetics and structural inheritance over successive generations. This was correlated with a major invasion deficiency at early stages of CEN2 knockdown, and replication defects at later stages. These results indicate that CEN2 is incorporated into multiple cytoskeletal structures to serve distinct functions that are required for parasite survival.

SUBMITTER: Leung JM

PROVIDER: S-EPMC6633390 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Centrin2 from the human parasite Toxoplasma gondii is required for its invasion and intracellular replication.

Leung Jacqueline M JM Liu Jun J Wetzel Laura A LA Hu Ke K

Journal of cell science 20190701 13

Centrins are EF-hand containing proteins ubiquitously found in eukaryotes and are key components of centrioles/basal bodies as well as certain contractile fibers. We previously identified three centrins in the human parasite Toxoplasma gondii, all of which localized to the centrioles. However, one of them, T. gondii (Tg) Centrin2 (CEN2), is also targeted to structures at the apical and basal ends of the parasite, as well as to annuli at the base of the apical cap of the membrane co ...[more]

PMID: 31182647

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Project description:Toxoplasma gondii and its Plasmodium kin share a well-conserved invasion process, including sequential secretion of adhesive molecules for host cell attachment and invasion. However, only a few orthologs have been shown to be important for efficient invasion by both genera. Bioinformatic screening to uncover potential new players in invasion identified a previously unrecognized T. gondii ortholog of Plasmodium glycosylphosphatidylinositol-anchored micronemal antigen (TgGAMA). We show that TgGAMA localizes to the micronemes and is processed into several proteolytic products within the parasite prior to secretion onto the parasite surface during invasion. TgGAMA from parasite lysate bound to several different host cell types in vitro, suggesting a role in parasite attachment. Consistent with this function, tetracycline-regulatable TgGAMA and TgGAMA knockout strains showed significant reductions in host cell invasion at the attachment step, with no defects in any of the other stages of the parasite lytic cycle. Together, the results of this work reveal a new conserved component of the adhesive repertoire of apicomplexan parasites. IMPORTANCE Toxoplasma gondii is a successful human pathogen in the same phylum as malaria-causing Plasmodium parasites. Invasion of a host cell is an essential process that begins with secretion of adhesive proteins onto the parasite surface for attachment and subsequent penetration of the host cell. Conserved invasion proteins likely play roles that were maintained through the divergence of these parasites. Here, we identify a new conserved invasion protein called glycosylphosphatidylinositol-anchored micronemal antigen (GAMA). Tachyzoites lacking TgGAMA were partially impaired in parasite attachment and invasion of host cells, yielding the first genetic evidence of a specific role in parasite entry into host cells. These findings widen our appreciation of the repertoire of conserved proteins that apicomplexan parasites employ for cell invasion.

Dataset Information

Centrin2 from the human parasite Toxoplasma gondii is required for its invasion and intracellular replication.

Publications

Centrin2 from the human parasite <i>Toxoplasma gondii</i> is required for its invasion and intracellular replication.

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