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Characterization of a MOB1 homolog in the Apicomplexan parasite toxoplasma gondii

Publication . Delgado, Inês L. S.; Tavares, Alexandra; Francisco, Samuel; Santos, Dulce; Coelho, João; Basto, Afonso P.; Zúquete, Sara; Müller, Joachim; Hemphill, Andrew; Meissner, Markus; Soares, Helena; Leitão, Alexandre; Nolasco, S.

Monopolar spindle One Binder1 (MOB1) proteins are conserved components of the tumor-suppressing Hippo pathway, regulating cellular processes such as cytokinesis. Apicomplexan parasites present a life cycle that relies on the parasites’ ability to differentiate between stages and regulate their proliferation; thus, Hippo signaling pathways could play an important role in the regulation of the apicomplexan life cycle. Here, we report the identification of one MOB1 protein in the apicomplexan Toxoplasma gondii. To characterize the function of MOB1, we generated gain-of-function transgenic lines with a ligand-controlled destabilization domain, and loss-of-function clonal lines obtained through CRISPR/Cas9 technology. Contrary to what has been characterized in other eukaryotes, MOB1 is not essential for cytokinesis in T. gondii. However, this picture is complex since we found MOB1 localized between the newly individualized daughter nuclei at the end of mitosis. Moreover, we detected a significant delay in the replication of overexpressing tachyzoites, contrasting with increased replication rates in knockout tachyzoites. Finally, using the proximity-biotinylation method, BioID, we identified novel members of the MOB1 interactome, a probable consequence of the observed lack of conservation of some key amino acid residues. Altogether, the results point to a complex evolutionary history of MOB1 roles in apicomplexans, sharing properties with other eukaryotes but also with divergent features, possibly associated with their complex life cycle.

2021-11Journal article

Open access

The apicomplexan parasite Toxoplasma gondii

Publication . Delgado, Inês L. S.; Zúquete, Sara; Santos, Dulce; Basto, Afonso P.; Leitão, Alexandre; Nolasco, Sofia

Toxoplasma gondii is a ubiquitous zoonotic parasite with an obligatory intracellular lifestyle. It relies on a specialized set of cytoskeletal and secretory organelles for host cell invasion. When infecting its felid definitive host, T. gondii undergoes sexual reproduction in the intestinal epithelium, producing oocysts that are excreted with the feces and sporulate in the environment. In other hosts and/or tissues, T. gondii multiplies by asexual reproduction. Rapidly dividing tachyzoites expand through multiple tissues, particularly nervous and muscular tissues, and eventually convert to slowly dividing bradyzoites which produce tissue cysts, structures that evade the immune system and remain infective within the host. Infection normally occurs through ingestion of sporulated oocysts or tissue cysts. While T. gondii is able to infect virtually all warm-blooded animals, most infections in humans are asymptomatic, with clinical disease occurring most often in immunocompromised hosts or fetuses carried by seronegative mothers that are infected during pregnancy.

2022-01Journal article

Open access