TgCentrin2 is required for invasion and replication in the human parasite Toxoplasma gondii

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, TgCentrin2 (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 TgCentrin2 plays in these locations was unknown. Here we report the functional characterization of TgCentrin2 using a conditional knockdown method that combines transcriptional and protein stability control. The knockdown resulted in an ordered loss of TgCentrin2 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 TgCentrin2 knockdown, and replication defects at later stages. These results indicate that TgCentrin2 is incorporated into multiple cytoskeletal structures to serve distinct functions in T. gondii required for parasite survival.