A SAS-6-Like Protein Suggests that the Toxoplasma Conoid Complex Evolved from Flagellar Components

Leon, Jessica Cruz de; Scheumann, Nicole; Beatty, Wandy L.; Beck, Josh R.; Tran, Johnson Q.; Yau, Candace; Bradley, Peter J.; Gull, Keith; Wickstead, Bill; Morrissette, Naomi S.

doi:10.1128/ec.00096-13

Cited by 75 publications

(111 citation statements)

References 87 publications

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“…A comprehensive analysis of centriole components conserved across eukaryotic organisms (12,13) showed that the T. brucei genome encodes a conserved SAS-6 homolog, which we named TbSAS-6 (Tb927.9.10550), in addition to a SAS-6-like protein (39). Despite a slightly larger size than its human homolog, TbSAS-6 contains two conserved motifs, a PISA (present in SAS-6) domain and a SAS-6 conserved domain 2, in its N terminus and four coiled-coil structures in the middle portion of the protein ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The Centriole Cartwheel Protein SAS-6 in Trypanosoma brucei Is Required for Probasal Body Biogenesis and Flagellum Assembly

Liu

Zhou

et al. 2015

Eukaryot Cell

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The centriole in eukaryotes functions as the cell's microtubule-organizing center (MTOC) to nucleate spindle assembly, and its biogenesis requires an evolutionarily conserved protein, SAS-6, which assembles the centriole cartwheel. Trypanosoma brucei, an early branching protozoan, possesses the basal body as its MTOC to nucleate flagellum biogenesis. However, little is known about the components of the basal body and their roles in basal body biogenesis and flagellum assembly. Here, we report that the T. brucei SAS-6 homolog, TbSAS-6, is localized to the mature basal body and the probasal body throughout the cell cycle. RNA interference (RNAi) of TbSAS-6 inhibited probasal body biogenesis, compromised flagellum assembly, and caused cytokinesis arrest. Surprisingly, overexpression of TbSAS-6 in T. brucei also impaired probasal body duplication and flagellum assembly, contrary to SAS-6 overexpression in humans, which produces supernumerary centrioles. Furthermore, we showed that depletion of T. brucei Polo-like kinase, TbPLK, or inhibition of TbPLK activity did not abolish TbSAS-6 localization to the basal body, in contrast to the essential role of Polo-like kinase in recruiting SAS-6 to centrioles in animals. Altogether, these results identified the essential role of TbSAS-6 in probasal body biogenesis and flagellum assembly and suggest the presence of a TbPLK-independent pathway governing basal body duplication in T. brucei.T rypanosoma brucei is an early branching microbial eukaryote and the causative agent of sleeping sickness in humans and nagana in cattle in sub-Saharan Africa. A trypanosome cell possesses a motile flagellum that is nucleated by the basal body, the cell's microtubule organizing center (MTOC), exits the cell body through the flagellar pocket, and is attached to the cell body along most of its length via a specialized cytoskeletal structure termed the flagellum attachment zone (FAZ). The flagellum is composed of a canonical 9 ϩ 2 microtubule axoneme and an extra-axoneme structure termed the paraflagellar rod (PFR), and it is required for cell morphogenesis, cell motility, and cytokinesis (1, 2). Early in the cell cycle, a trypanosome cell possesses a basal body, which nucleates the flagellum axoneme, and an associated probasal body. The probasal body matures to a basal body when the cell proceeds to S phase of the cell cycle; subsequently, two probasal bodies are formed, each of which associates with each of the two mature basal bodies (3, 4). A new flagellum then is assembled from the newly matured basal body, which then undergoes a rotation toward the posterior of the old basal body. Following the elongation of the new flagellum, the new basal body/probasal body pair moves toward the posterior portion of the cell, which constitutes one of the first cytoskeletal events in the cell cycle of T. brucei (3, 4). Movement of the basal body is required for cell morphogenesis (4) and for segregation of the kinetoplast, the cell's mitochondrial genome that is attached to the basal body through a struc...

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Section: Resultsmentioning

confidence: 99%

The Centriole Cartwheel Protein SAS-6 in Trypanosoma brucei Is Required for Probasal Body Biogenesis and Flagellum Assembly

Liu

Zhou

et al. 2015

Eukaryot Cell

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“…The presence of these proteins alone is therefore not linked to the origin of parasitism, and their roles in parasites and free-living relatives cannot be assessed without direct functional evidence. Several proteins associated with the apical complex itself belong to this category, including rhoptry and microneme proteins (SI Appendix, Table S4) and cytoskeletal SAS6L (36). If chrompodellid homologs of these proteins are associated with structures for invasion or feeding, it would support the homology of these structures and the apical complex (37).…”

Section: /Namentioning

confidence: 99%

Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives

Janouškovec

Tikhonenkov

Burki

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

181

189

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Apicomplexans are a major lineage of parasites, including causative agents of malaria and toxoplasmosis. How such highly adapted parasites evolved from free-living ancestors is poorly understood, particularly because they contain nonphotosynthetic plastids with which they have a complex metabolic dependency. Here, we examine the origin of apicomplexan parasitism by resolving the evolutionary distribution of several key characteristics in their closest free-living relatives, photosynthetic chromerids and predatory colpodellids. Using environmental sequence data, we describe the diversity of these apicomplexan-related lineages and select five species that represent this diversity for transcriptome sequencing. Phylogenomic analysis recovered a monophyletic lineage of chromerids and colpodellids as the sister group to apicomplexans, and a complex distribution of retention versus loss for photosynthesis, plastid genomes, and plastid organelles. Reconstructing the evolution of all plastid and cytosolic metabolic pathways related to apicomplexan plastid function revealed an ancient dependency on plastid isoprenoid biosynthesis, predating the divergence of apicomplexan and dinoflagellates. Similarly, plastid genome retention is strongly linked to the retention of two genes in the plastid genome, sufB and clpC, altogether suggesting a relatively simple model for plastid retention and loss. Lastly, we examine the broader distribution of a suite of molecular characteristics previously linked to the origins of apicomplexan parasitism and find that virtually all are present in their free-living relatives. The emergence of parasitism may not be driven by acquisition of novel components, but rather by loss and modification of the existing, conserved traits.A picomplexans are globally important parasites of humans and animals that include Plasmodium (malaria), Toxoplasma (toxoplasmosis), and Cryptosporidium (cryptosporidiosis). Their success as parasites rests on several highly specialized structures and systems that enable them to gain entry to and divide within cells or tissues of their hosts. These structures include the multimembrane pellicle, a relict nonphotosynthetic plastid (absent in Cryptosporidium), and the apical complex, which is made up of cytoskeletal and secretory elements (e.g., the conoid and rhoptries, respectively). Many specific characteristics of apicomplexans make attractive drug targets, and others may have played a key role in the origin of parasitism. Indeed, the question of apicomplexan origins has been of interest in general but is challenged by a paucity of comparable information from free-living relatives. Several apicomplexan relatives are known, some photosynthetic and others predatory (1, 2), but we lack a comprehensive understanding of their biology because they have either been discovered only recently, or are difficult to establish and maintain in culture. In general, photosynthetic apicomplexan relatives are referred to as chromerids (including Chromera and Vitrella) (1, 3) whereas predators...

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“…Centrioles and basal bodies are generally considered to be the same structure, although in Apicomplexa, the centriole (but not the basal body) has an unusual arrangement (15). Further evidence of the involvement of flagellar components in the apical complex was the characterization of a protein that locates to the basal plate of basal bodies in Trypanosoma brucei and to the apical end of the conoid in Toxoplasma (41). Significantly, all Apicomplexa have dispensed with flagella in life cycle stages that possess an apical complex.…”

Section: Discussionmentioning

confidence: 99%

“…The most intriguing feature of the apical complex of C. velia, given the recent findings on Toxoplasma (41,42), is that it is contemporaneous with the flagella in a single cell; in fact, there are multiple connections between the pseudoconoid and the anterior flagellum. A set of so-far-unidentified fibers connect the anterior flagellar groove to the apex of the pseudoconoid via an enigmatic coiled structure that resides beneath a protrusion of the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

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Evidence of Intraflagellar Transport and Apical Complex Formation in a Free-Living Relative of the Apicomplexa

et al. 2014

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bSince its first description, Chromera velia has attracted keen interest as the closest free-living relative of parasitic Apicomplexa. The life cycle of this unicellular alga is complex and involves a motile biflagellate form. Flagella are thought to be formed in the cytoplasm, a rare phenomenon shared with Plasmodium in which the canonical mode of flagellar assembly, intraflagellar transport, is dispensed with. Here we demonstrate the expression of intraflagellar transport components in C. velia, answering the question of whether this organism has the potential to assemble flagella via the canonical route. We have developed and characterized a culturing protocol that favors the generation of flagellate forms. From this, we have determined a marked shift in the mode of daughter cell production from two to four daughter cells per division as a function of time after passage. We conduct an ultrastructural examination of the C. velia flagellate form by using serial TEM and show that flagellar biogenesis in C. velia occurs prior to cytokinesis. We demonstrate a close association of the flagellar apparatus with a complex system of apical structures, including a micropore, a conoid, and a complex endomembrane system reminiscent of the apical complex of parasitic apicomplexans. Recent work has begun to elucidate the possible flagellar origins of the apical complex, and we show that in C. velia these structures are contemporaneous within a single cell and share multiple connections. We propose that C. velia therefore represents a vital piece in the puzzle of the origins of the apical complex.

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A SAS-6-Like Protein Suggests that the Toxoplasma Conoid Complex Evolved from Flagellar Components

Cited by 75 publications

References 87 publications

The Centriole Cartwheel Protein SAS-6 in Trypanosoma brucei Is Required for Probasal Body Biogenesis and Flagellum Assembly

The Centriole Cartwheel Protein SAS-6 in Trypanosoma brucei Is Required for Probasal Body Biogenesis and Flagellum Assembly

Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives

Evidence of Intraflagellar Transport and Apical Complex Formation in a Free-Living Relative of the Apicomplexa

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