<i>Toxoplasma</i>F-Box Protein 1 is Required for Daughter Cell Scaffold Function During Parasite Replication

Baptista, Carlos Gustavo; Lis, Agnieszka; Deng, Bowen; Dittmar, Ashley; West, Christopher M.; Blader, Ira J.

doi:10.1101/511386

Cited by 1 publication

(5 citation statements)

References 71 publications

(72 reference statements)

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“…Compared with the knowledge of metazoans, plants and fungi, our knowledge about FBPs in protozoan parasites is very limited. Previously, we identified 18 putative Toxoplasma FBPs and here describe the role of one of those FBPs, TgFBXL2 [40]. We confirmed the identification of TgFBXL2 as a FBP by demonstrating its interactions with core components of the SCF-E3 as well as multiple CSN subunits.…”

Section: Discussionsupporting

confidence: 73%

“…Earlier, we identified candidate F-box proteins by interrogating the Toxoplasma genome and TgSKP1 interactome and identified TgFBXL2 with medium confidence as a candidate TgSKP1 interacting protein [40]. TgFBXL2 (TGGT1_313200) contains 832 amino acids and has 12 LRR sequence motifs that are predicted to fold into a solenoidlike structure characteristic of substrate receptor domains found in many FBPs (Fig.…”

Section: Identification Of Tgfbxl2 As a Scf-e3 Subunitmentioning

confidence: 99%

“…S1). Upstream of the LRR motifs lies an F-box-like sequence that likely explains its presence in the TgSKP1 interactome [40]. Upstream of the F-box motif are two predicted nuclear localization signals.…”

Section: Identification Of Tgfbxl2 As a Scf-e3 Subunitmentioning

confidence: 99%

“…For all assays, parasites harvested from Toxoplasma-infected HFF monolayers were released by syringe lysis by passage through a 27-gauge needle followed by washing in serum-free medium. Synchronized invasion, replication, and plaquing assays were performed as described previously [40].…”

Section: Invasion Replication and Plaque Assaysmentioning

confidence: 99%

“…FBPs mediate protein ubiquitination by recruiting substrates to SKP1/Cullin-1/FBP/RBX1 containing E3 ubiquitin ligase (SCF-E3) complexes [32][33][34][35][36][37][38]. Previously, we identified 18 putative FBPs in the Toxoplasma genome and a CRISPR screen indicated that the Toxoplasma F-box Protein L2 (TgFBXL2) is the FBP most required for parasite fitness [39,40]. TgFBXL2 is one of two L-type F-box proteins in Toxoplasma that have a C-terminal region comprising a series of leucine-rich repeats (LRRs).…”

Section: Introductionmentioning

confidence: 99%

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Toxoplasma gondiiF-Box Protein L2 Silences Feline-Restricted Genes Necessary for Sexual Commitment

Baptista,

Hosking,

Gas-Pascual

et al. 2023

Preprint

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Toxoplasma gondiiis a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive hosts, and a wide range of animals, including humans, serve as intermediate hosts. When the transmissible bradyzoite stage is orally ingested by felids, they transform into merozoites that expand asexually, ultimately generating millions of gametes for the parasite sexual cycle. However, bradyzoites in intermediate hosts differentiate exclusively to disease-causing tachyzoites, which rapidly disseminate throughout the host. Though tachyzoites are well-studied, the molecular mechanisms governing transitioning between developmental stages are poorly understood. Each parasite stage can be distinguished by a characteristic transcriptional signature, with one signature being repressed during the other stages. Switching between stages requires substantial changes in the proteome, which is achieved in part by ubiquitination. F-box proteins mediate protein poly-ubiquitination by recruiting substrates to SKP1, Cullin-1, F-Box protein E3 ubiquitin ligase (SCF-E3) complexes. We have identified an F-box protein namedToxoplasma gondiiF-Box Protein L2 (TgFBXL2), which localizes to distinct nuclear sites. TgFBXL2 is stably engaged in an SCF-E3 complex that is surprisingly also associated with a COP9 signalosome complex that negatively regulates SCF-E3 function. At the cellular level, TgFBXL2-depleted parasites are severely defective in centrosome replication and daughter cell development. Most remarkable, RNA seq data show that TgFBXL2 conditional depletion induces the expression of genes necessary for sexual commitment. We suggest that TgFBXL2 is a latent guardian of sexual stage development inToxoplasmaand poised to remove conflicting proteins in response to an unknown trigger of sexual development.AUTHOR SUMMARYToxoplasma gondiiis a protozoan parasite that replicates sexually in felids and asexually in nearly all other mammals with each life stage having a specific transcriptional profile. When life stage specific transcription is not properly controlled, the parasite dies and therefore it’s important to understand what inhibits expression of sexual stage genes during asexual growth and vice versa. Here we identify a ubiquitin E3 ligase complex that inhibits sexual stage gene expression during asexual growth.

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Section: Discussionsupporting

confidence: 73%

Section: Identification Of Tgfbxl2 As a Scf-e3 Subunitmentioning

confidence: 99%

Section: Identification Of Tgfbxl2 As a Scf-e3 Subunitmentioning

confidence: 99%

Section: Invasion Replication and Plaque Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxoplasma gondiiF-Box Protein L2 Silences Feline-Restricted Genes Necessary for Sexual Commitment

Baptista,

Hosking,

Gas-Pascual

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

ToxoplasmaF-Box Protein 1 is Required for Daughter Cell Scaffold Function During Parasite Replication

Abstract: 24By binding to the adaptor protein SKP1 and serving as substrate receptors for the Skp1, 25

Cited by 1 publication

References 71 publications

Toxoplasma gondiiF-Box Protein L2 Silences Feline-Restricted Genes Necessary for Sexual Commitment

Toxoplasma gondiiF-Box Protein L2 Silences Feline-Restricted Genes Necessary for Sexual Commitment

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