{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:07:13Z","timestamp":1791508033674,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013886","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000}}],"reference-count":124,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006388","name":"H\u00c3\u00b4pitaux Universitaires de Gen\u00c3\u00a8ve","doi-asserted-by":"publisher","award":["HUG RC09-18"],"award-info":[{"award-number":["HUG RC09-18"]}],"id":[{"id":"10.13039\/501100006388","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00c3\u00b6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["TMAG-3_216166"],"award-info":[{"award-number":["TMAG-3_216166"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The Major Facilitator Superfamily (MFS) comprises a large and diverse group of membrane transport proteins involved in the translocation of metabolites across cellular membranes. The genome of\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    encodes approximately 60 putative MFS transporters, yet the functions of most remain poorly characterized. Conserved across the superphylum Alveolata, the inner membrane complex (IMC) is a specialized peripheral membrane system essential for parasite replication, structural integrity, motility, and host cell invasion. Here, we identify\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    Daughter Cell Transporter 1 (TgDCT1), a previously uncharacterized MFS transporter, as a critical regulator of daughter cell formation. TgDCT1 localizes predominantly to the daughter cell IMC and contains a predicted spinster-like MFS domain. Phylogenetic and structural analyses reveal that TgDCT1 is conserved across Alveolata, shares a canonical MFS fold with its\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    orthologue, and exhibits striking structural similarity to the human sphingosine-1-phosphate (S1P) transporter SPNS2, suggesting an evolutionarily conserved role in lipid transport. Conditional depletion of TgDCT1 results in severe defects in cytokinesis, including disrupted IMC architecture, aberrant daughter cell morphology, and failure of plasma membrane abscission. Although TgDCT1-depleted parasites retain the capacity for microneme secretion and egress, they display profoundly impaired motility and host cell invasion, ultimately leading to arrest of the lytic cycle. Notably, pharmacological inhibition of the S1P transporter SPNS2 using the compounds 11i and 33p phenocopies TgDCT1 depletion, impairing parasite morphogenesis, intracellular replication, and division synchrony. Furthermore, transgenic complementation demonstrates that the spinster-like domain of the\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    DCT1 orthologue can functionally substitute for TgDCT1, indicating that these transporters likely recognize the same substrate. Together, these findings establish TgDCT1 as a central regulator of lipid homeostasis required for IMC maturation, endodyogeny, and parasite propagation in\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    and likely other Apicomplexa.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013886","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T18:35:03Z","timestamp":1769625303000},"page":"e1013886","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Spinster-like Transporter at the Inner Membrane Complex is critical for Toxoplasma gondii cytokinesis, motility and invasion"],"prefix":"10.1371","volume":"22","author":[{"given":"Syrian G.","family":"Sanchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romuald","family":"Haase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Dubois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaux","family":"H\u00e9ritier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Humann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Hulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohumil","family":"Maco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Meister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Scapozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Vadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-2109","authenticated-orcid":true,"given":"Dominique","family":"Soldati-Favre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"issue":"1","key":"ppat.1013886.ref001","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cvfa.2021.11.009","article-title":"Cryptosporidiosis","volume":"38","author":"PRF Adkins","year":"2022","journal-title":"Vet Clin North Am Food Anim Pract"},{"issue":"1","key":"ppat.1013886.ref002","doi-asserted-by":"crossref","first-page":"2150456","DOI":"10.1080\/21505594.2022.2150456","article-title":"Pathogenicity and virulence of malaria: Sticky problems and tricky solutions","volume":"14","author":"IS Walker","year":"2023","journal-title":"Virulence"},{"issue":"11","key":"ppat.1013886.ref003","doi-asserted-by":"crossref","first-page":"968","DOI":"10.3390\/pathogens13110968","article-title":"Diseases caused by and behaviors associated with Toxoplasma gondii infection","volume":"13","author":"GKH Akins","year":"2024","journal-title":"Pathog"},{"issue":"9425","key":"ppat.1013886.ref004","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"JG Montoya","year":"2004","journal-title":"Lancet"},{"issue":"1","key":"ppat.1013886.ref005","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev-micro-091014-104100","article-title":"Lytic cycle of Toxoplasma gondii: 15 years later","volume":"69","author":"IJ Blader","year":"2015","journal-title":"Annu Rev Microbiol"},{"issue":"7","key":"ppat.1013886.ref006","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.ijmm.2018.07.007","article-title":"Secretory organelle trafficking in Toxoplasma gondii: A long story for a short travel","volume":"308","author":"K Venugopal","year":"2018","journal-title":"Int J Med Microbiol"},{"issue":"9","key":"ppat.1013886.ref007","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1242\/jcs.021089","article-title":"Organellar dynamics during the cell cycle of Toxoplasma gondii","volume":"121","author":"M Nishi","year":"2008","journal-title":"J Cell 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systematics and the origins of sporozoa and dinoflagellates (phylum myzozoa nom. nov.)","volume":"40","author":"T Cavalier-Smith","year":"2004","journal-title":"Eur J Protistol"},{"issue":"8","key":"ppat.1013886.ref012","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0169-5347(03)00152-6","article-title":"Morphostasis in alveolate evolution","volume":"18","author":"BS Leander","year":"2003","journal-title":"Trends Ecol Evol"},{"issue":"6","key":"ppat.1013886.ref013","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/molbev\/msn070","article-title":"Alveolins, a new family of cortical proteins that define the protist infrakingdom Alveolata","volume":"25","author":"SB Gould","year":"2008","journal-title":"Mol Biol Evol"},{"issue":"2","key":"ppat.1013886.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005403","article-title":"Gliding Associated Proteins Play Essential Roles during the Formation of the Inner Membrane Complex of Toxoplasma 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Engelberg","year":"2025","journal-title":"mBio"},{"issue":"15","key":"ppat.1013886.ref035","first-page":"3320","article-title":"Dynamics of the Toxoplasma gondii inner membrane complex","volume":"127","author":"DT Ouologuem","year":"2014","journal-title":"J Cell Sci"},{"issue":"1","key":"ppat.1013886.ref036","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1462-5822.2010.01514.x","article-title":"A family of intermediate filament-like proteins is sequentially assembled into the cytoskeleton of Toxoplasma gondii","volume":"13","author":"BR Anderson-White","year":"2011","journal-title":"Cell Microbiol"},{"issue":"7","key":"ppat.1013886.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007946","article-title":"Toxoplasma F-box protein 1 is required for daughter cell scaffold function during parasite replication","volume":"15","author":"CG Baptista","year":"2019","journal-title":"PLoS 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Back","year":"2023","journal-title":"mBio"},{"issue":"10","key":"ppat.1013886.ref041","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011707","article-title":"Identification of IMC43, a novel IMC protein that collaborates with IMC32 to form an essential daughter bud assembly complex in Toxoplasma gondii","volume":"19","author":"RR Pasquarelli","year":"2023","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1013886.ref042","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1012411","article-title":"BCC0 collaborates with IMC32 and IMC43 to form the Toxoplasma gondii essential daughter bud assembly complex","volume":"20","author":"RR Pasquarelli","year":"2024","journal-title":"PLoS Pathog"},{"issue":"8","key":"ppat.1013886.ref043","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0012354","article-title":"Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii","volume":"5","author":"MS 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Res"},{"issue":"1","key":"ppat.1013886.ref094","doi-asserted-by":"crossref","first-page":"2813","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"},{"issue":"10","key":"ppat.1013886.ref095","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.chembiol.2021.05.001","article-title":"Toxoplasma gondii serine hydrolases regulate parasite lipid mobilization during growth and replication within the host","volume":"28","author":"O Onguka","year":"2021","journal-title":"Cell Chem Biol"},{"issue":"1","key":"ppat.1013886.ref096","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/s42003-020-01480-5","article-title":"Phosphatidylinositol synthesis, its selective salvage, and inter-regulation of anionic phospholipids in Toxoplasma gondii","volume":"3","author":"B Ren","year":"2020","journal-title":"Commun Biol"},{"issue":"7","key":"ppat.1013886.ref097","doi-asserted-by":"crossref","first-page":"111224","DOI":"10.1016\/j.celrep.2022.111224","article-title":"Ceramide biosynthesis is critical for establishment of the intracellular niche of Toxoplasma gondii","volume":"40","author":"MA Nyonda","year":"2022","journal-title":"Cell Rep"},{"issue":"17","key":"ppat.1013886.ref098","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1038\/s44318-024-00171-9","article-title":"Cytokinetic abscission in Toxoplasma gondii is governed by protein phosphatase 2A and the daughter cell scaffold complex","volume":"43","author":"J-B Marq","year":"2024","journal-title":"EMBO J"},{"issue":"17","key":"ppat.1013886.ref099","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.261270","article-title":"The cortical microtubules of Toxoplasma gondii underlie the helicity of parasite movement","volume":"136","author":"IF Tengganu","year":"2023","journal-title":"J Cell 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Melatti","year":"2019","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1013886.ref103","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/mmi.14138","article-title":"TgDrpC, an atypical dynamin-related protein in Toxoplasma gondii, is associated with vesicular transport factors and parasite division","volume":"111","author":"I Heredero-Bermejo","year":"2019","journal-title":"Mol Microbiol"},{"issue":"8","key":"ppat.1013886.ref104","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0012302","article-title":"A Toxoplasma MORN1 null mutant undergoes repeated divisions but is defective in basal assembly, apicoplast division and cytokinesis","volume":"5","author":"A Lorestani","year":"2010","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1013886.ref105","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000754","article-title":"TgMORN1 is a key organizer for the basal complex of Toxoplasma gondii","volume":"6","author":"AT Heaslip","year":"2010","journal-title":"PLoS Pathog"},{"issue":"13","key":"ppat.1013886.ref106","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.228791","article-title":"Centrin2 from the human parasite Toxoplasma gondii is required for its invasion and intracellular replication","volume":"132","author":"JM Leung","year":"2019","journal-title":"J Cell Sci"},{"issue":"9","key":"ppat.1013886.ref107","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1093\/molbev\/mss081","article-title":"Evolution and architecture of the inner membrane complex in asexual and sexual stages of the malaria parasite","volume":"29","author":"M Kono","year":"2012","journal-title":"Mol Biol Evol"},{"key":"ppat.1013886.ref108","doi-asserted-by":"crossref","first-page":"611801","DOI":"10.3389\/fcimb.2020.611801","article-title":"The Dynamic Roles of the Inner Membrane Complex in the Multiple Stages of the Malaria Parasite","volume":"10","author":"JL Ferreira","year":"2021","journal-title":"Front Cell 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Bushell","year":"2017","journal-title":"Cell"},{"issue":"6388","key":"ppat.1013886.ref112","doi-asserted-by":"crossref","DOI":"10.1126\/science.aap7847","article-title":"Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis","volume":"360","author":"M Zhang","year":"2018","journal-title":"Science"},{"key":"ppat.1013886.ref113","doi-asserted-by":"crossref","first-page":"10519","DOI":"10.1038\/ncomms10519","article-title":"Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite","volume":"7","author":"S Kenthirapalan","year":"2016","journal-title":"Nat Commun"},{"issue":"4","key":"ppat.1013886.ref114","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","volume":"8","author":"BA Fox","year":"2009","journal-title":"Eukaryot 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