{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:18:52Z","timestamp":1790461132693,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology, India","award":["BT\/COE\/34\/SP15138\/2015"],"award-info":[{"award-number":["BT\/COE\/34\/SP15138\/2015"]}]},{"name":"Department of Biotechnology, India","award":["BT\/PR7976\/BRB\/10\/1223\/2013"],"award-info":[{"award-number":["BT\/PR7976\/BRB\/10\/1223\/2013"]}]},{"name":"Department of Science and Technology, India","award":["SB\/SO\/BB\/006\/2014"],"award-info":[{"award-number":["SB\/SO\/BB\/006\/2014"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-12-PDOC-0028- Project Apicolipid"],"award-info":[{"award-number":["ANR-12-PDOC-0028- Project Apicolipid"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-12-PDOC-0028- Project Apicolipid"],"award-info":[{"award-number":["ANR-12-PDOC-0028- Project Apicolipid"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-12-PDOC-0028- Project Apicolipid"],"award-info":[{"award-number":["ANR-12-PDOC-0028- Project Apicolipid"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Atip-Avenir and Finovi programs","award":["CNRS-INSERM-FinoviAtip-AvenirApicolipid projects"],"award-info":[{"award-number":["CNRS-INSERM-FinoviAtip-AvenirApicolipid projects"]}]},{"name":"the Atip-Avenir and Finovi programs","award":["CNRS-INSERM-FinoviAtip-AvenirApicolipid projects"],"award-info":[{"award-number":["CNRS-INSERM-FinoviAtip-AvenirApicolipid projects"]}]},{"name":"the Atip-Avenir and Finovi programs","award":["CNRS-INSERM-FinoviAtip-AvenirApicolipid projects"],"award-info":[{"award-number":["CNRS-INSERM-FinoviAtip-AvenirApicolipid projects"]}]},{"name":"Laboratoire d\u2019Excellence Parafrap","award":["ANR-11-LABX-0024"],"award-info":[{"award-number":["ANR-11-LABX-0024"]}]},{"name":"Laboratoire d\u2019Excellence Parafrap","award":["ANR-11-LABX-0024"],"award-info":[{"award-number":["ANR-11-LABX-0024"]}]},{"name":"Laboratoire d\u2019Excellence Parafrap","award":["ANR-11-LABX-0024"],"award-info":[{"award-number":["ANR-11-LABX-0024"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Apicomplexan parasites are causative agents of major human diseases. Calcium Dependent Protein Kinases (CDPKs) are crucial components for the intracellular development of apicomplexan parasites and are thus considered attractive drug targets. CDPK7 is an atypical member of this family, which initial characterization suggested to be critical for intracellular development of both\n                    <jats:italic>Apicomplexa Plasmodium falciparum<\/jats:italic>\n                    and\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    . However, the mechanisms via which it regulates parasite replication have remained unknown. We performed quantitative phosphoproteomics of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    lacking TgCDPK7 to identify its parasitic targets. Our analysis lead to the identification of several putative TgCDPK7 substrates implicated in critical processes like phospholipid (PL) synthesis and vesicular trafficking. Strikingly, phosphorylation of TgRab11a via TgCDPK7 was critical for parasite intracellular development and protein trafficking. Lipidomic analysis combined with biochemical and cellular studies confirmed that TgCDPK7 regulates phosphatidylethanolamine (PE) levels in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    . These studies provide novel insights into the regulation of these processes that are critical for parasite development by TgCDPK7.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009325","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T13:25:13Z","timestamp":1614345913000},"page":"e1009325","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8751-1369","authenticated-orcid":true,"given":"Priyanka","family":"Bansal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Antil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3896-166X","authenticated-orcid":true,"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9349-4411","authenticated-orcid":true,"given":"Yoshiki","family":"Yamaryo-Bott\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul Singh","family":"Rawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4322-5491","authenticated-orcid":true,"given":"Keshava K.","family":"Datta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7419-3410","authenticated-orcid":true,"given":"Nicholas J.","family":"Katris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-536X","authenticated-orcid":true,"given":"Cyrille Y.","family":"Bott\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6206-2384","authenticated-orcid":true,"given":"T. S. Keshava","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6861-0508","authenticated-orcid":true,"given":"Pushkar","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"issue":"3","key":"ppat.1009325.ref001","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","volume":"19","author":"HE Bullen","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"6","key":"ppat.1009325.ref002","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"},{"issue":"5980","key":"ppat.1009325.ref003","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1126\/science.1188191","article-title":"A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes","volume":"328","author":"JD Dvorin","year":"2010","journal-title":"Science"},{"issue":"5","key":"ppat.1009325.ref004","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1128\/AAC.02261-13","article-title":"Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs","volume":"58","author":"RY Gaji","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"29","key":"ppat.1009325.ref005","doi-asserted-by":"crossref","first-page":"20386","DOI":"10.1074\/jbc.M114.561670","article-title":"Regulation of Plasmodium falciparum development by calcium-dependent protein kinase 7 (PfCDPK7)","volume":"289","author":"P Kumar","year":"2014","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1009325.ref006","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41467-017-00053-1","article-title":"PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum","volume":"8","author":"S Kumar","year":"2017","journal-title":"Nat Commun"},{"issue":"7296","key":"ppat.1009325.ref007","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nature09022","article-title":"Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma","volume":"465","author":"S Lourido","year":"2010","journal-title":"Nature"},{"issue":"1","key":"ppat.1009325.ref008","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/cmi.12186","article-title":"The Toxoplasma gondii calcium-dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival","volume":"16","author":"J Morlon-Guyot","year":"2014","journal-title":"Cell Microbiol"},{"issue":"1","key":"ppat.1009325.ref009","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.chom.2012.05.014","article-title":"A Plasmodium calcium-dependent protein kinase controls zygote development and transmission by translationally activating repressed mRNAs","volume":"12","author":"S Sebastian","year":"2012","journal-title":"Cell Host Microbe"},{"issue":"4","key":"ppat.1009325.ref010","first-page":"503","article-title":"Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite","volume":"117","author":"O Billker","year":"2004"},{"issue":"6","key":"ppat.1009325.ref011","doi-asserted-by":"crossref","first-page":"e1004197","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"},{"issue":"8","key":"ppat.1009325.ref012","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1096\/fj.12-203877","article-title":"Novel insights into the regulation of malarial calcium-dependent protein kinase 1","volume":"26","author":"A Ahmed","year":"2012","journal-title":"FASEB J"},{"issue":"4","key":"ppat.1009325.ref013","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/S0955-0674(99)80067-2","article-title":"The role of ARF and Rab GTPases in membrane transport","volume":"11","author":"P Chavrier","year":"1999","journal-title":"Current opinion in cell biology"},{"issue":"3","key":"ppat.1009325.ref014","first-page":"759","volume":"77","author":"S Mukherjee","year":"1997","journal-title":"Endocytosis"},{"key":"ppat.1009325.ref015","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"D Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"ppat.1009325.ref016","doi-asserted-by":"crossref","first-page":"e1001029","DOI":"10.1371\/journal.ppat.1001029","article-title":"Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B","volume":"6","author":"C Agop-Nersesian","year":"2010","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1009325.ref017","doi-asserted-by":"crossref","first-page":"e1000270","DOI":"10.1371\/journal.ppat.1000270","article-title":"Rab11A-controlled assembly of the inner membrane complex is required for completion of apicomplexan cytokinesis","volume":"5","author":"C Agop-Nersesian","year":"2009","journal-title":"PLoS Pathog"},{"issue":"3","key":"ppat.1009325.ref018","doi-asserted-by":"crossref","first-page":"e1003213","DOI":"10.1371\/journal.ppat.1003213","article-title":"An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes","volume":"9","author":"K Kremer","year":"2013","journal-title":"PLoS Pathog"},{"issue":"5","key":"ppat.1009325.ref019","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.micinf.2008.01.017","article-title":"Comparative genomics of the Rab protein family in Apicomplexan parasites","volume":"10","author":"G Langsley","year":"2008","journal-title":"Microbes Infect"},{"issue":"1","key":"ppat.1009325.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yexcr.2014.07.027","article-title":"Rab proteins: the key regulators of intracellular vesicle transport","volume":"328","author":"T Bhuin","year":"2014","journal-title":"Experimental cell research"},{"issue":"12","key":"ppat.1009325.ref021","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/nmeth1132","article-title":"An FKBP destabilization domain modulates protein levels in Plasmodium falciparum","volume":"4","author":"CM Armstrong","year":"2007","journal-title":"Nature methods"},{"issue":"5","key":"ppat.1009325.ref022","doi-asserted-by":"crossref","first-page":"e1008106","DOI":"10.1371\/journal.ppat.1008106","article-title":"Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication","volume":"16","author":"K Venugopal","journal-title":"PLoS Pathog. 2020"},{"issue":"48","key":"ppat.1009325.ref023","doi-asserted-by":"crossref","first-page":"13882","DOI":"10.1021\/bi7011993","article-title":"Lipidomic analysis of Toxoplasma gondii reveals unusual polar lipids","volume":"46","author":"R Welti","year":"2007","journal-title":"Biochemistry"},{"issue":"10","key":"ppat.1009325.ref024","doi-asserted-by":"crossref","first-page":"6809","DOI":"10.1074\/jbc.M113.509406","article-title":"Phosphatidylethanolamine synthesis in the parasite mitochondrion is required for efficient growth but dispensable for survival of Toxoplasma gondii","volume":"289","author":"A Hartmann","year":"2014","journal-title":"J Biol Chem"},{"issue":"22","key":"ppat.1009325.ref025","doi-asserted-by":"crossref","first-page":"15277","DOI":"10.1016\/S0021-9258(19)49529-X","article-title":"Phosphatidylethanolamine is the donor of the ethanolamine residue linking a glycosylphosphatidylinositol anchor to protein","volume":"267","author":"AK Menon","year":"1992","journal-title":"J Biol Chem"},{"issue":"10","key":"ppat.1009325.ref026","doi-asserted-by":"crossref","first-page":"9222","DOI":"10.1074\/jbc.M310502200","article-title":"The Plasmodium falciparum PfGatp is an endoplasmic reticulum membrane protein important for the initial step of malarial glycerolipid synthesis","volume":"279","author":"TC Santiago","year":"2004","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1009325.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2006.02.047","article-title":"Cytokinesis in plant and animal cells: endosomes \u2019shut the door\u2019","volume":"294","author":"F Baluska","year":"2006","journal-title":"Developmental biology"},{"issue":"2","key":"ppat.1009325.ref028","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/boc.201100062","article-title":"Rab11 is phosphorylated by classical and novel protein kinase C isoenzymes upon sustained phorbol ester activation","volume":"104","author":"M Pavarotti","year":"2012","journal-title":"Biology of the cell"},{"issue":"4","key":"ppat.1009325.ref029","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.plipres.2013.06.003","article-title":"Lipid synthesis in protozoan parasites: a comparison between kinetoplastids and apicomplexans","volume":"52","author":"S Ramakrishnan","year":"2013","journal-title":"Prog Lipid Res"},{"issue":"8","key":"ppat.1009325.ref030","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"},{"issue":"1","key":"ppat.1009325.ref031","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/mmi.13694","article-title":"TgPL2, a patatin-like phospholipase domain-containing protein, is involved in the maintenance of apicoplast lipids homeostasis in Toxoplasma","volume":"105","author":"MF Leveque","year":"2017","journal-title":"Mol Microbiol"},{"issue":"1","key":"ppat.1009325.ref032","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12633","article-title":"Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast","volume":"19","author":"MJ Shears","year":"2017","journal-title":"Cell Microbiol"},{"issue":"7","key":"ppat.1009325.ref033","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1074\/jbc.M111.310144","article-title":"Apicoplast and endoplasmic reticulum cooperate in fatty acid biosynthesis in apicomplexan parasite Toxoplasma gondii","volume":"287","author":"S Ramakrishnan","year":"2012","journal-title":"J Biol Chem"},{"issue":"9","key":"ppat.1009325.ref034","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":"Nature methods"},{"key":"ppat.1009325.ref035","doi-asserted-by":"crossref","first-page":"D561","DOI":"10.1093\/nar\/gkq973","article-title":"The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored","volume":"39","author":"D Szklarczyk","year":"2011","journal-title":"Nucleic Acids Res"},{"issue":"24","key":"ppat.1009325.ref036","doi-asserted-by":"crossref","first-page":"14010","DOI":"10.1074\/jbc.271.24.14010","article-title":"Insertional tagging, cloning, and expression of the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase gene. Use as a selectable marker for stable transformation","volume":"271","author":"RG Donald","year":"1996","journal-title":"J Biol Chem"},{"issue":"4","key":"ppat.1009325.ref037","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"},{"issue":"11","key":"ppat.1009325.ref038","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.1096\/fj.14-252569","article-title":"Structure of Toxoplasma gondii coronin, an actin-binding protein that relocalizes to the posterior pole of invasive parasites and contributes to invasion and egress","volume":"28","author":"J Salamun","year":"2014","journal-title":"FASEB J"},{"issue":"3","key":"ppat.1009325.ref039","doi-asserted-by":"crossref","first-page":"e01114","DOI":"10.1128\/mBio.01114-14","article-title":"Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR\/CAS9","volume":"5","author":"B Shen","year":"2014","journal-title":"MBio"},{"issue":"5","key":"ppat.1009325.ref040","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.chom.2012.09.013","article-title":"Mitochondrial metabolism of glucose and glutamine is required for intracellular growth of Toxoplasma gondii","volume":"12","author":"JI MacRae","year":"2012","journal-title":"Cell Host Microbe"},{"issue":"16","key":"ppat.1009325.ref041","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1021\/jf300147y","article-title":"Quantification of phosphatidic acid in foodstuffs using a thin-layer-chromatography-imaging technique","volume":"60","author":"T Tanaka","year":"2012","journal-title":"Journal of agricultural and food chemistry"},{"issue":"8","key":"ppat.1009325.ref042","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"EG Bligh","year":"1959","journal-title":"Canadian journal of biochemistry and physiology"},{"issue":"6897","key":"ppat.1009325.ref043","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nature00946","article-title":"Golgi biogenesis in Toxoplasma gondii","volume":"418","author":"L Pelletier","year":"2002","journal-title":"Nature"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T13:26:15Z","timestamp":1614345975000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009325"}},"subtitle":[],"editor":[{"given":"Kami","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009325","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,26]]}}}