Towards a molecular architecture of the centrosome in Toxoplasma gondii

Abstract

Toxoplasma gondii is the causative agent of toxoplasmosis. The pathogenicity of this unicellular parasite is tightly linked to its ability to efficiently proliferate within its host. Tachyzoites, the fast dividing form of the parasite, divide by endodyogeny. This process involves a single round of DNA replication, closed nuclear mitosis, and assembly of two daughter cells within a mother. The successful completion of endodyogeny relies on the temporal and spatial coordination of a plethora of simultaneous events. It has been shown that the Toxoplasma centrosome serves as signaling hub which nucleates spindle microtubules during mitosis and organizes the scaffolding of daughter cells components during cytokinesis. In addition, the centrosome is essential for inheriting both the apicoplast (a chloroplast-like organelle) and the Golgi apparatus. A growing body of evidence supports the notion that the T. gondii centrosome diverges in protein composition, structure and organization from its counterparts in higher eukaryotes making it an attractive source of potentially druggable targets. Here, we summarize the current knowledge on T. gondii centrosomal proteins and extend the putative centrosomal protein repertoire by in silico identification of mammalian centrosomal protein orthologs. We propose a working model for the organization and architecture of the centrosome in Toxoplasma parasites. Experimental validation of our proposed model will uncover how each predicted protein translates into the biology of centrosome, cytokinesis, karyokinesis, and organelle inheritance in Toxoplasma parasites. K E Y W O R D Scentrosome, endodyogeny, parasite, Plasmodium falciparum, Toxoplasma gondii

A coiled-coil protein is required for coordination of karyokinesis and cytokinesis in Toxoplasma gondii

“…In animal cells, the centrosome copy restriction is mainly achieved through the polo kinase PLK4, which regulates the recruitment of SAS6 to the centriole together with CEP192 and CEP152 (Fujita, Yoshino, & Chiba, ). However, homologues for PLK4, CEP192, CEP152, or STIL (a protein partner of SAS6) were not found in apicomplexan genomes (Morlon‐Guyot et al, ), suggesting that the regulation of centriole formation is performed by other proteins and pathways in these parasites. Protein targets of this kinase are not known, but its putative localisation at the PCM may point toward the phosphorylation of proteins located in this area, indicating a role in outer core centrosome copy restriction for the T. gondii PCM.…”

“…The T. gondii centrioles are arranged in parallel fashion, and their size is smaller than that of the mammalian centrioles (Dubremetz, ; Francia & Striepen, ). Moreover, a comprehensive bioinformatics search of eukaryotic centrosome protein homologues in apicomplexan genomes revealed that several of the eukaryotic centrosome components are missing in the T. gondii genome (Morlon‐Guyot, Francia, Dubremetz, & Daher, ). This highlights the possibility of the unique composition of the centrosome in apicomplexan parasites.…”

“…Unfortunately, none of the targets of these proteins have been identified so far, illustrating the lack of knowledge of the components of the T. gondii centrosome. An initial study discovered TgCEP250 and TgCEP250L‐1 as new components of the centrosome (Suvorova et al, ), and a comprehensive bioinformatics search revealed little conservation of the human centrosome proteins in T. gondii (Morlon‐Guyot et al, ), indicating the specific composition of the parasite centrosome and PCM.…”

TgCep250 is dynamically processed through the division cycle and essential for structural integrity of the Toxoplasma centrosome

“…Phosphorylation of C-NAP1/Cep250 by NIMA kinase Nek2 promotes degradation of C-NAP1/Cep250 and results in splitting of the linked centrosomes 21 . Reciprocal BLAST analysis suggests that C-NAP1/Cep250 and rootletin orthologs are absent from the Toxoplasma genome 6 , however, the regulatory machinery might be conserved.…”

“…For example, the centrioles are composed of nine singlet microtubules, smaller in size than mammalian centrioles, and the centriole pair is arranged in parallel rather than perpendicular 4 . Orthologs of many key components in the mammalian centrosome cannot be found in the Toxoplasma genome 6 . Even without canonical protein orthologs, recent studies have shown that a group of coiled-coil proteins localize to the centrosome and support proper karyokinesis and cytokinesis 7–8 .…”