{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:23:06Z","timestamp":1784956986709,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010901","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["NIH - R01AI123457"],"award-info":[{"award-number":["NIH - R01AI123457"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["NIH - R01AI123457"],"award-info":[{"award-number":["NIH - R01AI123457"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["FC001189 via Francis Crick Institute"],"award-info":[{"award-number":["FC001189 via Francis Crick Institute"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["FC001189 via Francis Crick Institute"],"award-info":[{"award-number":["FC001189 via Francis Crick Institute"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["FC001189 via Francis Crick Institute"],"award-info":[{"award-number":["FC001189 via Francis Crick Institute"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010438","name":"Francis Crick Institute","doi-asserted-by":"publisher","award":["FC001999"],"award-info":[{"award-number":["FC001999"]}],"id":[{"id":"10.13039\/100010438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2 0 4 9 0 9 \/ Z \/ 1 6 \/ Z)"],"award-info":[{"award-number":["2 0 4 9 0 9 \/ Z \/ 1 6 \/ Z)"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation pour la recherche medicale","award":["FRM, EQU202103012700"],"award-info":[{"award-number":["FRM, EQU202103012700"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR - 21 - CE44 - 0010 - 01"],"award-info":[{"award-number":["ANR - 21 - CE44 - 0010 - 01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010115","name":"R\u00e9gion Auvergne-Rh\u00f4ne-Alpes","doi-asserted-by":"publisher","award":["AuRA IRICE GEMELI)"],"award-info":[{"award-number":["AuRA IRICE GEMELI)"]}],"id":[{"id":"10.13039\/501100010115","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finovi program","award":["Apicoplipid Project"],"award-info":[{"award-number":["Apicoplipid Project"]}]},{"name":"Laboratoire d\u2019Excellence Parafrap","award":["ANR - 11 - LABX - 0024"],"award-info":[{"award-number":["ANR - 11 - LABX - 0024"]}]},{"name":"LIA - IRP CNRS","award":["Apicolipid project"],"award-info":[{"award-number":["Apicolipid project"]}]},{"name":"CEFIPRA - MESRI","award":["Project 60 03 - 1"],"award-info":[{"award-number":["Project 60 03 - 1"]}]},{"name":"IDEX Universit\u00e9 Grenoble-Alpes"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Fundamental processes that govern the lytic cycle of the intracellular parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    are regulated by several signalling pathways. However, how these pathways are connected remains largely unknown. Here, we compare the phospho-signalling networks during\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    egress from its host cell by artificially raising cGMP or calcium levels. We show that both egress inducers trigger indistinguishable signalling responses and provide evidence for a positive feedback loop linking calcium and cyclic nucleotide signalling. Using WT and conditional knockout parasites of the non-essential calcium-dependent protein kinase 3 (CDPK3), which display a delay in calcium inonophore-mediated egress, we explore changes in phosphorylation and lipid signalling in sub-minute timecourses after inducing Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release. These studies indicate that cAMP and lipid metabolism are central to the feedback loop, which is partly dependent on CDPK3 and allows the parasite to respond faster to inducers of egress. Biochemical analysis of 4 phosphodiesterases (PDEs) identified in our phosphoproteomes establishes PDE2 as a cAMP-specific PDE which regulates Ca\n                    <jats:sup>2+<\/jats:sup>\n                    induced egress in a CDPK3-independent manner. The other PDEs display dual hydrolytic activity and play no role in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    induced egress. In summary, we uncover a positive feedback loop that enhances signalling during egress, thereby linking several signalling pathways.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010901","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T14:42:55Z","timestamp":1666276975000},"page":"e1010901","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signalling in calcium-induced Toxoplasma gondii egress"],"prefix":"10.1371","volume":"18","author":[{"given":"Stephanie D.","family":"Nofal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caia","family":"Dominicus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Broncel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Katris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen R.","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Arrizabalaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille Y.","family":"Bott\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon M.","family":"Invergo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-6657","authenticated-orcid":true,"given":"Moritz","family":"Treeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ppat.1010901.ref001","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.ijpara.2009.04.003","article-title":"Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis","volume":"39","author":"G Pappas","year":"2009","journal-title":"Int J Parasitol"},{"key":"ppat.1010901.ref002","doi-asserted-by":"crossref","first-page":"41492","DOI":"10.1074\/jbc.M106154200","article-title":"The loss of cytoplasmic potassium upon host cell breakdown triggers egress of Toxoplasma gondii","volume":"276","author":"R Moudy","year":"2001","journal-title":"J Biol Chem"},{"key":"ppat.1010901.ref003","doi-asserted-by":"crossref","first-page":"e1004488","DOI":"10.1371\/journal.ppat.1004488","article-title":"Acidification Activates Toxoplasma gondii Motility and Egress by Enhancing Protein Secretion and Cytolytic Activity","volume":"10","author":"MS Roiko","year":"2014","journal-title":"PLoS Pathog"},{"key":"ppat.1010901.ref004","doi-asserted-by":"crossref","first-page":"9554","DOI":"10.1074\/jbc.M115.700518","article-title":"Serum albumin stimulates protein kinase G-dependent microneme secretion in Toxoplasma gondii","volume":"291","author":"KM Brown","year":"2016","journal-title":"J Biol Chem"},{"key":"ppat.1010901.ref005","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41564-018-0339-8","article-title":"Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform","volume":"4","author":"H Bisio","year":"2019","journal-title":"Nat Microbiol"},{"key":"ppat.1010901.ref006","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1550-7408.1987.tb03177.x","article-title":"Effects of Extracellular Potassium on Acid Release and Motility Initiation in Toxoplasma gondii","volume":"34","author":"T Endo","year":"1987","journal-title":"J Protozool"},{"key":"ppat.1010901.ref007","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.15252\/embj.201796794","article-title":"Crosstalk between PKA and PKG controls pH -dependent host cell egress of Toxoplasma gondii","volume":"36","author":"Y Jia","year":"2017","journal-title":"EMBO J"},{"key":"ppat.1010901.ref008","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.chom.2016.02.006","article-title":"Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma Article Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma","author":"HE Bullen","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"3","key":"ppat.1010901.ref009","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ceca.2014.12.010","article-title":"The Calcium Signaling Toolkit of the Apicomplexan Parasites Toxoplasma gondii and Plasmodium spp","volume":"57","author":"S Lourido","year":"2015","journal-title":"Cell Calcium"},{"key":"ppat.1010901.ref010","doi-asserted-by":"crossref","first-page":"25870","DOI":"10.1074\/jbc.M202553200","article-title":"Toxoplasma gondii microneme secretion involves intracellular Ca2+ release from inositol 1,4,5-triphosphate (IP3)\/ryanodine-sensitive stores","volume":"277","author":"JL Lovett","year":"2002","journal-title":"J Biol Chem"},{"key":"ppat.1010901.ref011","first-page":"2158","article-title":"InsP3 Signaling in Apicomplexan Parasites","volume":"17","author":"CRS Garcia","year":"2017","journal-title":"Curr Top Med Chem"},{"key":"ppat.1010901.ref012","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.chom.2009.05.017","article-title":"Calcium-Dependent Signaling and Kinases in Apicomplexan Parasites","volume":"5","author":"O Billker","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ppat.1010901.ref013","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1126\/science.1210829","article-title":"A DOC2 Protein Identified by Mutational Profiling is Essential for Apicomplexan Parasite Exocytosis","volume":"335","author":"A Farrell","year":"2012","journal-title":"Science"},{"key":"ppat.1010901.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1001806","article-title":"Phosphoinositide Metabolism Links cGMP-Dependent Protein Kinase G to Essential Ca 2 + Signals at Key Decision Points in the Life Cycle of Malaria Parasites","volume":"12","author":"M Brochet","year":"2014","journal-title":"PLoS Biol"},{"key":"ppat.1010901.ref015","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00375-17","article-title":"Plasma membrane association by N-acylation governs PKG function in Toxoplasma gondii","volume":"8","author":"KM Brown","year":"2017","journal-title":"MBio"},{"key":"ppat.1010901.ref016","article-title":"Protein kinase A negatively regulates Ca 2+ signalling in Toxoplasma gondii","author":"AD Uboldi","year":"2018","journal-title":"PLoS Biology"},{"key":"ppat.1010901.ref017","article-title":"Functional Analysis of the Expanded Phosphodiesterase Gene Family in Toxoplasma gondii Tachyzoites","volume":"7","author":"WJ Moss","year":"2022","journal-title":"mSphere"},{"key":"ppat.1010901.ref018","doi-asserted-by":"crossref","first-page":"e1000941","DOI":"10.1371\/journal.ppat.1000941","article-title":"Protein Kinase A Dependent Phosphorylation of Apical Membrane Antigen 1 Plays an Important Role in Erythrocyte Invasion by the Malaria Parasite","volume":"6","author":"K Leykauf","year":"2010","journal-title":"PLoS Pathog"},{"key":"ppat.1010901.ref019","article-title":"Phosphodiesterase beta is the master regulator of camp signalling during malaria parasite invasion","author":"C Flueck","year":"2019","journal-title":"PLoS Biology"},{"key":"ppat.1010901.ref020","article-title":"Cyclic AMP signalling controls key components of malaria parasite host cell invasion machinery","author":"A Patel","year":"2019","journal-title":"PLoS Biology"},{"key":"ppat.1010901.ref021","doi-asserted-by":"crossref","first-page":"4524","DOI":"10.1038\/emboj.2012.299","article-title":"Distinct signalling pathways control Toxoplasma egress and host-cell invasion","volume":"31","author":"S Lourido","year":"2012","journal-title":"EMBO J"},{"key":"ppat.1010901.ref022","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1128\/IAI.01173-15","article-title":"Analysis of noncanonical calciumdependent protein kinases in Toxoplasma gondii by targeted gene deletion using CRISPR\/Cas9","volume":"84","author":"S Long","year":"2016","journal-title":"Infect Immun"},{"key":"ppat.1010901.ref023","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1128\/MMBR.64.3.607-623.2000","article-title":"Lytic Cycle of Toxoplasma gondii","volume":"64","author":"MW Black","year":"2000","journal-title":"Microbiol Mol Biol Rev"},{"key":"ppat.1010901.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003049","article-title":"A Forward Genetic Screen Reveals that Calcium-dependent Protein Kinase 3 Regulates Egress in Toxoplasma","volume":"8","author":"E Garrison","year":"2012","journal-title":"PLoS Pathog"},{"key":"ppat.1010901.ref025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003066","article-title":"TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells","volume":"8","author":"JM McCoy","year":"2012","journal-title":"PLoS Pathog"},{"key":"ppat.1010901.ref026","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12685","article-title":"Analysis of Ca2+ mediated signaling regulating Toxoplasma infectivity reveals complex relationships between key molecules","volume":"19","author":"RJ Stewart","year":"2017","journal-title":"Cell Microbiol"},{"key":"ppat.1010901.ref027","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1021\/cb501004q","article-title":"Identification of potent phosphodiesterase inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites","volume":"10","author":"BL Howard","year":"2015","journal-title":"ACS Chem Biol"},{"key":"ppat.1010901.ref028","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrm2822","article-title":"The nuts and bolts of AGC protein kinases","volume":"11","author":"LR Pearce","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ppat.1010901.ref029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.00130-18","article-title":"Calcium-Dependent Protein Kinase 5 Is Required for Release of Egress-Specific Organelles in Plasmodium falciparum","volume":"9","author":"S Absalon","year":"2018","journal-title":"MBio"},{"key":"ppat.1010901.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2021.728425","article-title":"An Extracellular Redox Signal Triggers Calcium Release and Impacts the Asexual Development of Toxoplasma gondii","volume":"11","author":"E Alves","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"ppat.1010901.ref031","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.chom.2018.10.015","article-title":"Essential cGMP Signaling in Toxoplasma Is Initiated by a Hybrid P-Type ATPase-Guanylate Cyclase","volume":"24","author":"KM Brown","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ppat.1010901.ref032","doi-asserted-by":"crossref","first-page":"e201900402","DOI":"10.26508\/lsa.201900402","article-title":"An unusual and vital protein with guanylate cyclase and P4-ATPase domains in a pathogenic protist","volume":"2","author":"\u00d6 G\u00fcnay-Esiyok","year":"2019","journal-title":"Life Sci Alliance"},{"key":"ppat.1010901.ref033","doi-asserted-by":"crossref","first-page":"8959","DOI":"10.1074\/jbc.RA118.005491","article-title":"An apically located hybrid guanylate cyclase-ATPase is critical for the initiation of Ca2+ signaling and motility in Toxoplasma gondii","volume":"294","author":"L Yang","year":"2019","journal-title":"J Biol Chem"},{"key":"ppat.1010901.ref034","first-page":"22","article-title":"The apical annuli of Toxoplasma gondii are composed of coiled-coil and signalling proteins embedded in the inner membrane complex sutures","author":"K Engelberg","year":"2020","journal-title":"Cell Microbiol"},{"key":"ppat.1010901.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004197","article-title":"The Calcium-Dependent Protein Kinase 3 of Toxoplasma Influences Basal Calcium Levels and Functions beyond Egress as Revealed by Quantitative Phosphoproteome Analysis","volume":"10","author":"M Treeck","year":"2014","journal-title":"PLoS Pathog"},{"key":"ppat.1010901.ref036","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/mmi.14156","article-title":"Characterisation of the Toxoplasma gondii tyrosine transporter and its phosphorylation by the calcium-dependent protein kinase 3","volume":"111","author":"BA Wallbank","year":"2019","journal-title":"Mol Microbiol"},{"key":"ppat.1010901.ref037","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1016\/j.celrep.2017.10.071","article-title":"Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation","volume":"21","author":"BM Invergo","year":"2017","journal-title":"Cell Rep"},{"key":"ppat.1010901.ref038","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1021\/cb400115y","article-title":"Exploiting the unique ATP-binding pocket of toxoplasma calcium-dependent protein kinase 1 to identify its substrates","volume":"8","author":"S Lourido","year":"2013","journal-title":"ACS Chem Biol"},{"key":"ppat.1010901.ref039","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cmi.12749","article-title":"A novel dense granule protein, GRA41, regulates timing of egress and calcium sensitivity in Toxoplasma gondii","volume":"19","author":"KA LaFavers","year":"2017","journal-title":"Cell Microbiol"},{"key":"ppat.1010901.ref040","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1083\/jcb.200309097","article-title":"Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium\/hydrogen exchanger in calcium regulation","volume":"165","author":"G Arrizabalaga","year":"2004","journal-title":"J Cell Biol"},{"issue":"1","key":"ppat.1010901.ref041","first-page":"1382","article-title":"A Toxoplasma gondii protein with homology to intracellular type Na+ \/H+ Exchangers is important for osmoregulation and invasion","volume":"317","author":"ME Francia","year":"2005","journal-title":"Exp Cell Res"},{"key":"ppat.1010901.ref042","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00845-15","article-title":"Two essential light chains regulate the MyoA lever arm to promote toxoplasma gliding motility","volume":"6","author":"MJ Williams","year":"2015","journal-title":"MBio"},{"key":"ppat.1010901.ref043","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1042\/BJ20051393","article-title":"A Toxoplasma gondii phosphoinositide phospholipase C (TgPI-PLC) with high affinity for phosphatidylinositol","volume":"394","author":"J Fang","year":"2006","journal-title":"Biochem J"},{"key":"ppat.1010901.ref044","article-title":"Rapid kinetics of lipid second messengers controlled by a cGMP signalling network coordinates apical complex functions in Toxoplasma tachyzoites","author":"NJ Katris","year":"2020","journal-title":"bioRxiv"},{"key":"ppat.1010901.ref045","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1111\/tra.12081","article-title":"Global analysis of apicomplexan protein S-acyl transferases reveals an enzyme essential for invasion","volume":"14","author":"K Fr\u00e9nal","year":"2013","journal-title":"Traffic"},{"key":"ppat.1010901.ref046","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-22956-w","article-title":"Toxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage","volume":"12","author":"S Dass","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1010901.ref047","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1016\/j.csbj.2020.11.024","article-title":"The protozoan parasite Toxoplasma gondii encodes a gamut of phosphodiesterases during its lytic cycle in human cells","volume":"18","author":"KC Vo","year":"2020","journal-title":"Comput Struct Biotechnol J"},{"key":"ppat.1010901.ref048","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.80336","article-title":"Temporal and thermal profiling of the Toxoplasma proteome implicates parasite Protein Phosphatase 1 in the regulation of Ca2+-responsive pathways","volume":"11","author":"AL Herneisen","year":"2022","journal-title":"Elife"},{"key":"ppat.1010901.ref049","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41564-022-01104-0","article-title":"Screening the Toxoplasma kinome with high-throughput tagging identifies a regulator of invasion and egress","volume":"7","author":"TA Smith","year":"2022","journal-title":"Nat Microbiol"},{"key":"ppat.1010901.ref050","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1128\/EC.00357-08","article-title":"Efficient Gene Replacements in Toxoplasma gondii Strains Deficient for Nonhomologous End Joining \u2020","volume":"8","author":"BA Fox","year":"2009","journal-title":"Eukaryot Cell"},{"key":"ppat.1010901.ref051","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1128\/EC.00358-08","article-title":"Tagging of endogenous genes in a Toxoplasma gondii strain lacking Ku80","volume":"8","author":"MH Huynh","year":"2009","journal-title":"Eukaryot Cell"},{"key":"ppat.1010901.ref052","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1126\/science.8469986","article-title":"Transient transfection and expression in the obligate intracellular parasite Toxoplasma gondii","volume":"260","author":"D Soldati","year":"1993","journal-title":"Science"},{"key":"ppat.1010901.ref053","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cell.2006.01.056","article-title":"Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space","volume":"125","author":"I Coppens","year":"2006","journal-title":"Cell"},{"key":"ppat.1010901.ref054","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2164-15-350","article-title":"Toxoplasma gondii merozoite gene expression analysis with comparison to the life cycle discloses a unique expression state during enteric development","volume":"15","author":"MS Behnke","year":"2014","journal-title":"BMC Genomics"},{"key":"ppat.1010901.ref055","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/s41564-020-0702-4","article-title":"An exported kinase family mediates species-specific erythrocyte remodelling and virulence in human malaria","volume":"5","author":"H Davies","year":"2020","journal-title":"Nat Microbiol"},{"key":"ppat.1010901.ref056","doi-asserted-by":"crossref","first-page":"e1003331","DOI":"10.1371\/journal.ppat.1003331","article-title":"A Nucleotide Sugar Transporter Involved in Glycosylation of the Toxoplasma Tissue Cyst Wall Is Required for Efficient Persistence of Bradyzoites","volume":"9","author":"CE Caffaro","year":"2013","journal-title":"PLOS Pathog"},{"key":"ppat.1010901.ref057","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.50598","article-title":"Differential requirements for cyclase-associated protein (CAP) in actin-dependent processes of toxoplasma gondii","volume":"8","author":"A Hunt","year":"2019","journal-title":"Elife"},{"key":"ppat.1010901.ref058","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.cell.2016.08.019","article-title":"A Genome-Wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes","volume":"166","author":"SM Sidik","year":"2016","journal-title":"Cell"},{"key":"ppat.1010901.ref059","first-page":"1367","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"J Cox","year":"2008","journal-title":"Nat Biotechnol 2008 2612"},{"key":"ppat.1010901.ref060","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1021\/pr101065j","article-title":"Andromeda: a peptide search engine integrated into the MaxQuant environment","volume":"10","author":"J Cox","year":"2011","journal-title":"J Proteome Res"},{"key":"ppat.1010901.ref061","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: improving support for quantification data","volume":"47","author":"Y Perez-Riverol","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010901.ref062","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"S Tyanova","year":"2016","journal-title":"Nat Methods"},{"key":"ppat.1010901.ref063","doi-asserted-by":"crossref","first-page":"289","DOI":"10.32614\/RJ-2016-021","article-title":"mclust 5: Clustering, Classification and Density Estimation Using Gaussian Finite Mixture Models","volume":"8","author":"L Scrucca","year":"2016","journal-title":"R J"},{"key":"ppat.1010901.ref064","first-page":"1","article-title":"GOATOOLS: A Python library for Gene Ontology analyses","volume":"8","author":"Klopfenstein D V.","year":"2018","journal-title":"Sci Reports 2018 81"},{"key":"ppat.1010901.ref065","first-page":"531","article-title":"MIMP: predicting the impact of mutations on kinase-substrate phosphorylation.","volume":"12","author":"O Wagih","year":"2015","journal-title":"Nat Methods 2015 126"},{"key":"ppat.1010901.ref066","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1101\/gr.849004","article-title":"WebLogo: a sequence logo generator","volume":"14","author":"GE Crooks","year":"2004","journal-title":"Genome Res"},{"key":"ppat.1010901.ref067","doi-asserted-by":"crossref","first-page":"e1005765","DOI":"10.1371\/journal.ppat.1005765","article-title":"Apicoplast-Localized Lysophosphatidic Acid Precursor Assembly Is Required for Bulk Phospholipid Synthesis in Toxoplasma gondii and Relies on an Algal\/Plant-Like Glycerol 3-Phosphate Acyltransferase","volume":"12","author":"S Amiar","year":"2016","journal-title":"PLOS Pathog"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010901","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010901","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T13:33:01Z","timestamp":1667309581000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010901"}},"subtitle":[],"editor":[{"given":"Mathieu","family":"Brochet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":67,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010901","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.11.29.470317","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,20]]}}}