{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:31:09Z","timestamp":1780525869721,"version":"3.54.1"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 31672543"],"award-info":[{"award-number":["No. 31672543"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Zhejiang Province \u201cSannongliufang\u201d Science and Technology Cooperation Project","award":["No. 2020SNLF007"],"award-info":[{"award-number":["No. 2020SNLF007"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The mitochondrion is proposed as an ideal target organelle for the control of apicomplexan parasites, whose integrity depends on well-controlled protein import, folding, and turnover. The ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) was found to be associated with the mitochondrial integrity in <jats:italic>Toxoplasma gondii<\/jats:italic>. However, little is known about the roles and mechanisms of UBLCP1 in this apicomplexan parasite.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The subcellular localization of UBLCP1 in the tachyzoites of <jats:italic>T. gondii<\/jats:italic> was determined by an indirect immunofluorescence assay. The roles of UBLCP1 in the growth, cell cycle, and division of <jats:italic>T. gondii<\/jats:italic> were assessed by knocking out this molecule in the tachyzoites. Comparative phosphoproteomics between the UBLCP1-deficient and wild-type tachyzoites were performed to understand the roles of UBLCP1 in <jats:italic>T. gondii<\/jats:italic>. The virulence of UBLCP1-deficient tachyzoites of <jats:italic>T. gondii<\/jats:italic> was tested in mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>UBLCP1 is expressed in the nucleus and cytoplasm of <jats:italic>T. gondii<\/jats:italic> tachyzoites. Tachyzoites lacking UBLCP1 exhibit collapsed mitochondrion, decreased mitochondrial membrane potential, and compromised growth and proliferation in vitro. Proteins involved in protein turnover and intracellular trafficking have been found differentially phosphorylated in the UBLCP1-deficient tachyzoites compared with the control. Deletion of UBLCP1 also shows that this phosphatase is essential for the propagation and virulence of <jats:italic>T. gondii<\/jats:italic> tachyzoites. Mice immunized with UBLCP1-deficient <jats:italic>T. gondii<\/jats:italic> tachyzoites survived challenges with the virulent PRU or VEG strain.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>UBLCP1 is required for the mitochondrial integrity and essential in the lytic cycle (e.g., host cell invasion and parasite replication) in vitro and the pathogenicity of this parasite in vivo. UBLCP1 is a candidate target for a vaccine or a drug for toxoplasmosis in animals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s13071-025-06766-3","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:47:08Z","timestamp":1743223628000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phosphatase UBLCP1 is required for the growth, virulence and mitochondrial integrity of Toxoplasma gondii"],"prefix":"10.1186","volume":"18","author":[{"given":"Kaiyin","family":"Sheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyue","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"6766_CR1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","volume":"363","author":"JG Montoya","year":"2004","unstructured":"Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965\u201376.","journal-title":"Lancet"},{"key":"6766_CR2","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.pt.2019.07.001","volume":"35","author":"S Lourido","year":"2019","unstructured":"Lourido S. Toxoplasma gondii. Trends Parasitol. 2019;35:944\u20135.","journal-title":"Trends Parasitol"},{"key":"6766_CR3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1128\/CMR.11.2.267","volume":"11","author":"JP Dubey","year":"1998","unstructured":"Dubey JP, Lindsay DS, Speer CA. Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev. 1998;11:267\u201399.","journal-title":"Clin Microbiol Rev"},{"key":"6766_CR4","volume":"12","author":"JMJ Verhoef","year":"2021","unstructured":"Verhoef JMJ, Meissner M, Kooij TWA. Organelle dynamics in apicomplexan parasites. MBio. 2021;12:e0140921.","journal-title":"MBio"},{"key":"6766_CR5","first-page":"10","volume":"34","author":"HM Elsheikha","year":"2021","unstructured":"Elsheikha HM, Marra CM, Zhu XQ. Epidemiology, pathophysiology, diagnosis, and management of cerebral toxoplasmosis. Clin Microbiol Rev. 2021;34:10.","journal-title":"Clin Microbiol Rev"},{"key":"6766_CR6","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/S0140-6736(98)08220-8","volume":"353","author":"D Dunn","year":"1999","unstructured":"Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R. Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counselling. Lancet. 1999;353:1829\u201333.","journal-title":"Lancet"},{"key":"6766_CR7","first-page":"389","volume":"8","author":"ZD Wang","year":"2017","unstructured":"Wang ZD, Liu HH, Ma ZX, Ma HY, Li ZY, Yang ZB, et al. Toxoplasma gondii infection in immunocompromised patients: a systematic review and meta-analysis. Front Microbiol. 2017;8:389.","journal-title":"Front Microbiol"},{"key":"6766_CR8","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1046\/j.1365-2958.1999.01515.x","volume":"33","author":"IK Srivastava","year":"1999","unstructured":"Srivastava IK, Morrisey JM, Darrouzet E, Daldal F, Vaidya AB. Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Mol Microbiol. 1999;33:704\u201311.","journal-title":"Mol Microbiol"},{"key":"6766_CR9","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.parint.2014.09.011","volume":"64","author":"JE Siregar","year":"2015","unstructured":"Siregar JE, Kurisu G, Kobayashi T, Matsuzaki M, Sakamoto K, Mi-ichi F, et al. Direct evidence for the atovaquone action on the Plasmodium cytochrome bc1 complex. Parasitol Int. 2015;64:295\u2013300.","journal-title":"Parasitol Int"},{"key":"6766_CR10","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.pt.2008.07.004","volume":"24","author":"F Seeber","year":"2008","unstructured":"Seeber F, Limenitakis J, Soldati-Favre D. Apicomplexan mitochondrial metabolism: a story of gains, losses and retentions. Trends Parasitol. 2008;24:468\u201378.","journal-title":"Trends Parasitol"},{"key":"6766_CR11","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","volume":"20","author":"JB Spinelli","year":"2018","unstructured":"Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018;20:745\u201354.","journal-title":"Nat Cell Biol"},{"key":"6766_CR12","doi-asserted-by":"crossref","first-page":"42746","DOI":"10.1038\/srep42746","volume":"7","author":"J Ovciarikova","year":"2017","unstructured":"Ovciarikova J, Lemgruber L, Stilger KL, Sullivan WJ, Sheiner L. Mitochondrial behaviour throughout the lytic cycle of Toxoplasma gondii. Sci Rep. 2017;7:42746.","journal-title":"Sci Rep"},{"key":"6766_CR13","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1242\/jcs.021089","volume":"121","author":"M Nishi","year":"2008","unstructured":"Nishi M, Hu K, Murray JM, Roos DS. Organellar dynamics during the cell cycle of Toxoplasma gondii. J Cell Sci. 2008;121:1559\u201368.","journal-title":"J Cell Sci"},{"key":"6766_CR14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.mi.48.100194.000501","volume":"48","author":"JE Feagin","year":"1994","unstructured":"Feagin JE. The extrachromosomal DNAs of apicomplexan parasites. Annu Rev Microbiol. 1994;48:81\u2013104.","journal-title":"Annu Rev Microbiol"},{"key":"6766_CR15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0020-7519(99)00190-3","volume":"30","author":"JE Feagin","year":"2000","unstructured":"Feagin JE. Mitochondrial genome diversity in parasites. Int J Parasitol. 2000;30:371\u201390.","journal-title":"Int J Parasitol"},{"key":"6766_CR16","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41580-020-0210-7","volume":"21","author":"M Giacomello","year":"2020","unstructured":"Giacomello M, Pyakurel A, Glytsou C, Scorrano L. The cell biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol. 2020;21:204\u201324.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"6766_CR17","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1091\/mbc.12.8.2245","volume":"12","author":"E Smirnova","year":"2001","unstructured":"Smirnova E, Griparic L, Shurland DL, van der Bliek AM. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell. 2001;12:2245\u201356.","journal-title":"Mol Biol Cell"},{"key":"6766_CR18","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1083\/jcb.200304040","volume":"163","author":"S Meeusen","year":"2003","unstructured":"Meeusen S, Nunnari J. Evidence for a two membrane-spanning autonomous mitochondrial DNA replisome. J Cell Biol. 2003;163:503\u201310.","journal-title":"J Cell Biol"},{"key":"6766_CR19","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.bbamcr.2006.03.007","volume":"1763","author":"T Kuroiwa","year":"2006","unstructured":"Kuroiwa T, Nishida K, Yoshida Y, Fujiwara T, Mori T, Kuroiwa H, et al. Structure, function and evolution of the mitochondrial division apparatus. Biochim Biophys Acta. 2006;1763:510\u201321.","journal-title":"Biochim Biophys Acta"},{"key":"6766_CR20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/mmi.13715","volume":"106","author":"C Yang","year":"2017","unstructured":"Yang C, Arrizabalaga G. The serine\/threonine phosphatases of apicomplexan parasites. Mol Microbiol. 2017;106:1\u201321.","journal-title":"Mol Microbiol"},{"key":"6766_CR21","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ijpara.2020.11.006","volume":"51","author":"RY Gaji","year":"2021","unstructured":"Gaji RY, Sharp AK, Brown AM. Protein kinases in Toxoplasma gondii. Int J Parasitol. 2021;51:415\u201329.","journal-title":"Int J Parasitol"},{"key":"6766_CR22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.02732-19","volume":"11","author":"K Jacobs","year":"2020","unstructured":"Jacobs K, Charvat R, Arrizabalaga G. Identification of Fis1 interactors in Toxoplasma gondii reveals a novel protein required for peripheral distribution of the mitochondrion. MBio. 2020;11:10.","journal-title":"MBio"},{"key":"6766_CR23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007512","volume":"15","author":"C Melatti","year":"2019","unstructured":"Melatti C, Pieperhoff M, Lemgruber L, Pohl E, Sheiner L, Meissner M. A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii. PLoS Pathog. 2019;15:e1007512.","journal-title":"PLoS Pathog"},{"key":"6766_CR24","doi-asserted-by":"crossref","first-page":"18649","DOI":"10.1073\/pnas.1113170108","volume":"108","author":"X Guo","year":"2011","unstructured":"Guo X, Engel JL, Xiao J, Tagliabracci VS, Wang X, Huang L, et al. UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity. P Proc Natl Acad Sci USA. 2011;108:18649\u201354.","journal-title":"P Proc Natl Acad Sci USA"},{"key":"6766_CR25","volume":"7","author":"S Sun","year":"2017","unstructured":"Sun S, Liu S, Zhang Z, Zeng W, Sun C, Tao T, et al. Phosphatase UBLCP1 controls proteasome assembly. Open Biol. 2017;7:170042.","journal-title":"Open Biol"},{"key":"6766_CR26","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1073\/pnas.1912531117","volume":"117","author":"X Liu","year":"2020","unstructured":"Liu X, Xiao W, Zhang Y, Wiley SE, Zuo T, Zheng Y, et al. Reversible phosphorylation of Rpn1 regulates 26S proteasome assembly and function. Proc Natl Acad Sci USA. 2020;117:328\u201336.","journal-title":"Proc Natl Acad Sci USA"},{"key":"6766_CR27","doi-asserted-by":"crossref","first-page":"109888","DOI":"10.1016\/j.vetpar.2023.109888","volume":"315","author":"Y Yang","year":"2023","unstructured":"Yang Y, Yao C, Chen X, Sheng K, Zhao M, Yao C, et al. Redundant targeting signals of the apicoplast-resident protein TgMnmA in Toxoplasma gondii involve trans-organellar function. Vet Parasitol. 2023;315:109888.","journal-title":"Vet Parasitol"},{"key":"6766_CR28","volume":"11","author":"M Zhao","year":"2023","unstructured":"Zhao M, Yang Y, Shi Y, Chen X, Yang Y, Pan L, et al. PP2Ac\u03b1-B\u2019\/PR61 holoenzyme of Toxoplasma gondii is required for the amylopectin metabolism and proliferation of tachyzoites. Microbiol Spectr. 2023;11:e0010423.","journal-title":"Microbiol Spectr"},{"key":"6766_CR29","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0166-6851(00)00324-8","volume":"111","author":"C Toursel","year":"2000","unstructured":"Toursel C, Dzierszinski F, Bernigaud A, Mortuaire M, Tomavo S. Molecular cloning, organellar targeting and developmental expression of mitochondrial chaperone HSP60 in Toxoplasma gondii. Mol Biochem Parasitol. 2000;111:319\u201332.","journal-title":"Mol Biochem Parasitol"},{"key":"6766_CR30","doi-asserted-by":"crossref","first-page":"19335","DOI":"10.1074\/jbc.M116.725069","volume":"291","author":"GG van Dooren","year":"2016","unstructured":"van Dooren GG, Yeoh LM, Striepen B, McFadden GI. The import of proteins into the mitochondrion of Toxoplasma gondii. J Biol Chem. 2016;291:19335\u201350.","journal-title":"J Biol Chem"},{"key":"6766_CR31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004504","volume":"10","author":"K Fr\u00e9nal","year":"2014","unstructured":"Fr\u00e9nal K, Marq JB, Jacot D, Polonais V, Soldati-Favre D. Plasticity between MyoC- and MyoA-glideosomes: an example of functional compensation in Toxoplasma gondii invasion. PLoS Pathog. 2014;10:e1004504.","journal-title":"PLoS Pathog"},{"key":"6766_CR32","doi-asserted-by":"crossref","first-page":"41240","DOI":"10.1074\/jbc.M205056200","volume":"277","author":"T Mann","year":"2002","unstructured":"Mann T, Gaskins E, Beckers C. Proteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii. J Biol Chem. 2002;277:41240\u20136.","journal-title":"J Biol Chem"},{"key":"6766_CR33","volume":"6","author":"JR Beck","year":"2010","unstructured":"Beck JR, Rodriguez-Fernandez IA, de Leon JC, Huynh MH, Carruthers VB, Morrissette NS, et al. A novel family of Toxoplasma IMC proteins displays a hierarchical organization and functions in coordinating parasite division. PLoS Pathog. 2010;6:e1001094.","journal-title":"PLoS Pathog"},{"key":"6766_CR34","doi-asserted-by":"crossref","first-page":"947039","DOI":"10.3389\/fcimb.2022.947039","volume":"12","author":"Y Yang","year":"2022","unstructured":"Yang Y, Lin M, Chen X, Zhao X, Chen L, Zhao M, et al. The first apicoplast tRNA thiouridylase plays a vital role in the growth of Toxoplasma gondii. Front Cell Infect Microbiol. 2022;12:947039.","journal-title":"Front Cell Infect Microbiol"},{"key":"6766_CR35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-1-4939-6472-7_6","volume":"1498","author":"B Shen","year":"2017","unstructured":"Shen B, Brown K, Long S, Sibley LD. Development of CRISPR\/Cas9 for efficient genome editing in Toxoplasma gondii. Methods Mol Biol. 2017;1498:79\u2013103.","journal-title":"Methods Mol Biol"},{"key":"6766_CR36","first-page":"e01114","volume":"5","author":"B Shen","year":"2014","unstructured":"Shen B, Brown KM, Lee TD, Sibley LD. Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR\/CAS9. MBio. 2014;5:e01114-e1214.","journal-title":"MBio"},{"key":"6766_CR37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13567-023-01261-y","volume":"55","author":"J Xia","year":"2024","unstructured":"Xia J, Yang Y, Chen X, Song K, Ma G, Yang Y, et al. An apicoplast-localized deubiquitinase contributes to the cell growth and apicoplast homeostasis of Toxoplasma gondii. Vet Res. 2024;55:10.","journal-title":"Vet Res"},{"key":"6766_CR38","volume":"19","author":"QL Liang","year":"2023","unstructured":"Liang QL, Nie LB, Elsheikha HM, Li TT, Sun LX, Zhang ZW, et al. The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence. PLoS Pathog. 2023;19:e1011831.","journal-title":"PLoS Pathog"},{"key":"6766_CR39","volume":"18","author":"N Xia","year":"2022","unstructured":"Xia N, Guo X, Guo Q, Gupta N, Ji N, Shen B, et al. Metabolic flexibilities and vulnerabilities in the pentose phosphate pathway of the zoonotic pathogen Toxoplasma gondii. PLoS Pathog. 2022;18:e1010864.","journal-title":"PLoS Pathog"},{"key":"6766_CR40","doi-asserted-by":"crossref","first-page":"738794","DOI":"10.3389\/fcell.2021.738794","volume":"9","author":"QL Liang","year":"2021","unstructured":"Liang QL, Nie LB, Li TT, Elsheikha HM, Sun LX, Zhang ZW, et al. Functional characterization of 17 protein serine\/threonine phosphatases in Toxoplasma gondii using CRISPR-Cas9 system. Front Cell Dev Biol. 2021;9:738794.","journal-title":"Front Cell Dev Biol"},{"key":"6766_CR41","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s00018-022-04556-z","volume":"79","author":"J Yang","year":"2022","unstructured":"Yang J, Yang X, Liu A, Li Y, Niu Z, Lyu C, et al. The beta subunit of AMP-activated protein kinase is critical for cell cycle progression and parasite development in Toxoplasma gondii. Cell Mol Life Sci. 2022;79:532.","journal-title":"Cell Mol Life Sci"},{"key":"6766_CR42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009301","volume":"17","author":"AE Maclean","year":"2021","unstructured":"Maclean AE, Bridges HR, Silva MF, Ding S, Ovciarikova J, Hirst J, et al. Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex. PLoS Pathog. 2021;17:e1009301.","journal-title":"PLoS Pathog"},{"key":"6766_CR43","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1074\/jbc.M112.436378","volume":"288","author":"MR Duncan","year":"2013","unstructured":"Duncan MR, Fullerton M, Chaudhuri M. Tim50 in Trypanosoma brucei possesses a dual specificity phosphatase activity and is critical for mitochondrial protein import. J Biol Chem. 2013;288:3184\u201397.","journal-title":"J Biol Chem"},{"key":"6766_CR44","volume":"6","author":"K Yu","year":"2020","unstructured":"Yu K, Tian H, Deng H. PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion. Sci Adv. 2020;6:eabd0276.","journal-title":"Sci Adv"},{"key":"6766_CR45","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1038\/nprot.2016.136","volume":"11","author":"S Tyanova","year":"2016","unstructured":"Tyanova S, Temu T, Cox J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat Protoc. 2016;11:2301\u201319.","journal-title":"Nat Protoc"},{"key":"6766_CR46","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1093\/bib\/bbx117","volume":"20","author":"MY Galperin","year":"2019","unstructured":"Galperin MY, Kristensen DM, Makarova KS, Wolf YI, Koonin EV. Microbial genome analysis: the COG approach. Brief Bioinform. 2019;20:1063\u201370.","journal-title":"Brief Bioinform"},{"key":"6766_CR47","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.3389\/fimmu.2018.01814","volume":"9","author":"N Xia","year":"2018","unstructured":"Xia N, Zhou T, Liang X, Ye S, Zhao P, Yang J, et al. A lactate fermentation mutant of Toxoplasma stimulates protective immunity against acute and chronic toxoplasmosis. Front Immunol. 2018;9:1814.","journal-title":"Front Immunol"},{"key":"6766_CR48","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev-micro-091014-104100","volume":"69","author":"IJ Blader","year":"2015","unstructured":"Blader IJ, Coleman BI, Chen CT, Gubbels MJ. Lytic cycle of Toxoplasma gondii: 15 years later. Annu Rev Microbiol. 2015;69:463\u201385.","journal-title":"Annu Rev Microbiol"},{"key":"6766_CR49","first-page":"279","volume":"129","author":"M Oancea","year":"2006","unstructured":"Oancea M, Mazumder S, Crosby ME, Almasan A. Apoptosis assays. Methods Mol Med. 2006;129:279\u201390.","journal-title":"Methods Mol Med"},{"key":"6766_CR50","doi-asserted-by":"crossref","first-page":"5924","DOI":"10.1038\/s41598-019-42441-1","volume":"9","author":"C Yang","year":"2019","unstructured":"Yang C, Broncel M, Dominicus C, Sampson E, Blakely WJ, Treeck M, et al. A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells. Sci Rep. 2019;9:5924.","journal-title":"Sci Rep"},{"key":"6766_CR51","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1008771","volume":"16","author":"J Mayoral","year":"2020","unstructured":"Mayoral J, Tomita T, Tu V, Aguilan JT, Sidoli S, Weiss LM. Toxoplasma gondii PPM3C, a secreted protein phosphatase, affects parasitophorous vacuole effector export. PLoS Pathog. 2020;16:e1008771.","journal-title":"PLoS Pathog"},{"key":"6766_CR52","doi-asserted-by":"crossref","first-page":"7560","DOI":"10.1038\/s41467-022-35267-5","volume":"13","author":"JL Wang","year":"2022","unstructured":"Wang JL, Li TT, Elsheikha HM, Liang QL, Zhang ZW, Wang M, et al. The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii. Nat Commun. 2022;13:7560.","journal-title":"Nat Commun"},{"key":"6766_CR53","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s13071-024-06135-6","volume":"17","author":"XT Wu","year":"2024","unstructured":"Wu XT, Gao XW, Wang QQ, He K, Bilal MS, Dong H, et al. The plant-like protein phosphatase PPKL regulates parasite replication and morphology in Toxoplasma gondii. Parasit Vectors. 2024;17:142.","journal-title":"Parasit Vectors"},{"key":"6766_CR54","volume":"14","author":"C Yang","year":"2023","unstructured":"Yang C, Doud EH, Sampson E, Arrizabalaga G. The protein phosphatase PPKL is a key regulator of daughter parasite development in Toxoplasma gondii. MBio. 2023;14:e0225423.","journal-title":"MBio"},{"key":"6766_CR55","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature02083","volume":"42","author":"X Li","year":"2003","unstructured":"Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK, et al. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature. 2003;42:247\u201354.","journal-title":"Nature"},{"key":"6766_CR56","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41398-023-02702-0","volume":"13","author":"J Soueid","year":"2023","unstructured":"Soueid J, Hamze Z, Bedran J, Chahrour M, Boustany RM. A novel autism-associated UBLCP1 mutation impacts proteasome regulation\/activity. Transl Psychiatry. 2023;13:404.","journal-title":"Transl Psychiatry"},{"key":"6766_CR57","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.cell.2016.08.019","volume":"166","author":"SM Sidik","year":"2016","unstructured":"Sidik SM, Huet D, Ganesan SM, Huynh MH, Wang T, Nasamu AS, et al. A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes. Cell. 2016;166:1423-35.e12.","journal-title":"Cell"},{"key":"6766_CR58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-394309-5.00001-8","volume":"298","author":"B Anderson-White","year":"2012","unstructured":"Anderson-White B, Beck JR, Chen CT, Meissner M, Bradley PJ, Gubbels MJ. Cytoskeleton assembly in Toxoplasma gondii cell division. Int Rev Cell Mol Biol. 2012;298:1\u201331.","journal-title":"Int Rev Cell Mol Biol"},{"key":"6766_CR59","volume":"23","author":"C Wang","year":"2021","unstructured":"Wang C, Hu D, Tang X, Song X, Wang S, Zhang S, et al. Internal daughter formation of Toxoplasma gondii tachyzoites is coordinated by transcription factor TgAP2IX-5. Cell Microbiol. 2021;23:e13291.","journal-title":"Cell Microbiol"},{"key":"6766_CR60","volume":"14","author":"F Fan","year":"2023","unstructured":"Fan F, Xue L, Yin X, Gupta N, Shen B. AP2XII-1 is a negative regulator of merogony and presexual commitment in Toxoplasma gondii. MBio. 2023;14:e0178523.","journal-title":"MBio"},{"key":"6766_CR61","volume":"14","author":"PS Back","year":"2023","unstructured":"Back PS, Moon AS, Pasquarelli RR, Bell HN, Torres JA, Chen AL, et al. IMC29 plays an important role in Toxoplasma endodyogeny and reveals new components of the daughter-enriched IMC proteome. MBio. 2023;14:e0304222.","journal-title":"MBio"},{"key":"6766_CR62","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.3390\/ijms23115995","volume":"23","author":"L Vigetti","year":"2022","unstructured":"Vigetti L, Labour\u00e9 T, Roum\u00e9gous C, Cannella D, Touquet B, Mayer C, et al. The BCC7 protein contributes to the Toxoplasma basal pole by interfacing between the MyoC motor and the IMC membrane network. Int J Mol Sci. 2022;23:5995.","journal-title":"Int J Mol Sci"},{"key":"6766_CR63","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011707","volume":"19","author":"RR Pasquarelli","year":"2023","unstructured":"Pasquarelli RR, Back PS, Sha J, Wohlschlegel JA, Bradley PJ. Identification of IMC43, a novel IMC protein that collaborates with IMC32 to form an essential daughter bud assembly complex in Toxoplasma gondii. PLoS Pathog. 2023;19:e1011707.","journal-title":"PLoS Pathog"},{"key":"6766_CR64","volume":"10","author":"J Wang","year":"2014","unstructured":"Wang J, Dixon SE, Ting LM, Liu TK, Jeffers V, Croken MM, et al. Lysine acetyltransferase GCN5b interacts with AP2 factors and is required for Toxoplasma gondii proliferation. PLoS Pathog. 2014;10:e1003830.","journal-title":"PLoS Pathog"},{"key":"6766_CR65","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1146\/annurev-micro-090817-062741","volume":"72","author":"K Kim","year":"2018","unstructured":"Kim K. The epigenome, cell cycle, and development in Toxoplasma. Annu Rev Microbiol. 2018;72:479\u201399.","journal-title":"Annu Rev Microbiol"},{"key":"6766_CR66","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nature09022","volume":"465","author":"S Lourido","year":"2010","unstructured":"Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature. 2010;465:359\u201362.","journal-title":"Nature"},{"key":"6766_CR67","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/cmi.12186","volume":"16","author":"J Morlon-Guyot","year":"2014","unstructured":"Morlon-Guyot J, Berry L, Chen CT, Gubbels MJ, Lebrun M, Daher W. The Toxoplasma gondii calcium-dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival. Cell Microbiol. 2014;16:95\u2013114.","journal-title":"Cell Microbiol"},{"key":"6766_CR68","volume":"14","author":"MM Usey","year":"2023","unstructured":"Usey MM, Huet D. ATP synthase-associated coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing proteins are critical for mitochondrial function in Toxoplasma gondii. MBio. 2023;14:e0176923.","journal-title":"MBio"},{"key":"6766_CR69","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011566","volume":"19","author":"B Asady","year":"2023","unstructured":"Asady B, Sampels V, Romano JD, Levitskaya J, Lige B, Khare P, et al. Function and regulation of a steroidogenic CYP450 enzyme in the mitochondrion of Toxoplasma gondii. PLoS Pathog. 2023;19:e1011566.","journal-title":"PLoS Pathog"}],"container-title":["Parasites &amp; Vectors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-025-06766-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13071-025-06766-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-025-06766-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:49:10Z","timestamp":1743223750000},"score":1,"resource":{"primary":{"URL":"https:\/\/parasitesandvectors.biomedcentral.com\/articles\/10.1186\/s13071-025-06766-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6766"],"URL":"https:\/\/doi.org\/10.1186\/s13071-025-06766-3","relation":{},"ISSN":["1756-3305"],"issn-type":[{"value":"1756-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]},"assertion":[{"value":"12 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experimental animals used in this study were approved by the Experimental Animal Ethics Committee of Zhejiang University (approval no. ZJU201308-1-10-072). All experiments were carried out following the Guidelines for the Use of Experimental Animals of the People\u2019s Republic of China.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"122"}}