Essential Functions of Calmodulin and Identification of Its Proximal Interacting Proteins in Tachyzoite-Stage Toxoplasma gondii via BioID Technology

Song, Yang; Li, Longjiao; Mo, Xinyu; Pan, Ming; Shen, Bang; Fang, Rui; Hu, Min; Zhao, Junlong; Zhou, Yanqin

doi:10.1128/spectrum.01363-22

Cited by 3 publications

(2 citation statements)

References 59 publications

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“…Moreover, upon deletion of TgPP6C, two proteins were differentially phosphorylated (TGGT1_289100, HOOK and TGGT1_290160, SORTLR), which are involved in the parasite invasion, egress and virulence [28,29]. Some differentially phosphorylated proteins contribute to the division of T. gondii, including IMC proteins (IMC10, IMC14 and IMC29), IMC related proteins (ISP2, GAP40, GAPM2B and GAPM3), phosphatidic acid phosphatase (TGGT1_230690, LIPIN), myosin-specific co-chaperone of the UCS family (TGGT1_249480, UNC), cyclase associated protein (TGGT1_310030, CAP) and calmodulin (TGGT1_249240, CaM) [30][31][32][33][34][35][36][37][38][39][40][41][42] (Fig 6C and Table 1). The nucleus, cytosol and IMC were the main predicted locations for most of the differentially phosphorylated proteins based on the spatial data obtained from hyper LOPIT [43] (Fig 6D and S4 Table ).…”

Section: Plos Pathogensmentioning

confidence: 99%

The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence

Liang,

Nie,

Elsheikha

et al. 2023

PLoS Pathog

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Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite’s daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.

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Section: Plos Pathogensmentioning

confidence: 99%

The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence

Liang,

Nie,

Elsheikha

et al. 2023

PLoS Pathog

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“…Song et al utilized BioID to identify more than 300 proximal interacting proteins of calmodulin (CaM) in T. gondii. CaM was found to play essential roles in tachyzoite proliferation, invasion, and egress, with potential functions related to ion binding and oxidation reduction [92].…”

Section: Bira*-mediated Proximity-dependent Biotin Identification (Bi...mentioning

confidence: 99%

Proteomics Applications in Toxoplasma gondii: Unveiling the Host–Parasite Interactions and Therapeutic Target Discovery

Deng,

Vanagas,

Alonso

et al. 2023

Pathogens

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Toxoplasma gondii, a protozoan parasite with the ability to infect various warm-blooded vertebrates, including humans, is the causative agent of toxoplasmosis. This infection poses significant risks, leading to severe complications in immunocompromised individuals and potentially affecting the fetus through congenital transmission. A comprehensive understanding of the intricate molecular interactions between T. gondii and its host is pivotal for the development of effective therapeutic strategies. This review emphasizes the crucial role of proteomics in T. gondii research, with a specific focus on host–parasite interactions, post-translational modifications (PTMs), PTM crosstalk, and ongoing efforts in drug discovery. Additionally, we provide an overview of recent advancements in proteomics techniques, encompassing interactome sample preparation methods such as BioID (BirA*-mediated proximity-dependent biotin identification), APEX (ascorbate peroxidase-mediated proximity labeling), and Y2H (yeast two hybrid), as well as various proteomics approaches, including single-cell analysis, DIA (data-independent acquisition), targeted, top-down, and plasma proteomics. Furthermore, we discuss bioinformatics and the integration of proteomics with other omics technologies, highlighting its potential in unraveling the intricate mechanisms of T. gondii pathogenesis and identifying novel therapeutic targets.

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Proteomics Applications in <em>Toxoplasma gondii</em>: Unveiling the Host-Parasite Interactions and Therapeutic Target Discovery

Deng,

Vanagas,

Angel

2023

Preprint

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Toxoplasma gondii, a protozoan parasite with the ability to infect various warm-blooded vertebrates, including humans, is the causative agent of toxoplasmosis. This infection poses significant risks, leading to severe complications in immunocompromised individuals and potentially affecting the fetus through congenital transmission. A comprehensive understanding of the intricate molecular interactions between T. gondii and its host is pivotal for the development of effective therapeutic strategies. This review emphasizes the crucial role of proteomics in T. gondii research, with a specific focus on host-parasite interactions, post-translational modifications (PTMs), PTM crosstalk, and ongoing efforts in drug discovery. Additionally, we provide an overview of recent advancements in proteomics techniques, encompassing interactome sample preparation methods such as BioID, APEX, and Y2H, as well as various proteomics approaches, including single-cell analysis, DIA, targeted, top-down, and plasma proteomics. Furthermore, we discuss the integration of proteomics with other omics technologies, highlighting its potential in unraveling the intricate mechanisms of T. gondii pathogenesis and identifying novel therapeutic targets.

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Essential Functions of Calmodulin and Identification of Its Proximal Interacting Proteins in Tachyzoite-Stage Toxoplasma gondii via BioID Technology

Abstract: Toxoplasma gondii is an intracellular pathogen that threatens human and animal health. This unicellular parasite is active in many biological processes, such as egress and invasion.

Cited by 3 publications

References 59 publications

The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence

The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence

Proteomics Applications in Toxoplasma gondii: Unveiling the Host–Parasite Interactions and Therapeutic Target Discovery

Proteomics Applications in <em>Toxoplasma gondii</em>: Unveiling the Host-Parasite Interactions and Therapeutic Target Discovery

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