A Spinster-like Transporter at the Inner Membrane Complex is critical for Toxoplasma gondii cytokinesis, motility and invasion

Article Article scientifique Article A Spinster-like Transporter at the Inner Membrane Complex is critical for Toxoplasma gondii cytokinesis, motility and invasion eng 2026-01-28 2026 author Sanchez Syrian 419110 Département de microbiologie et médecine moléculaire (MIMOL) author Haase Romuald 949609 Département de microbiologie et médecine moléculaire (MIMOL) author Dubois David Jean 855464 author Heritier Margaux 835570 author Humann Rachel 428609 Département de microbiologie et médecine moléculaire (MIMOL) author Hulo Nicolas 29577 Administration de la section de biologie (BIAD) author Maco Bohumil 0000-0001-8444-313X 863802 Services communs de la faculté de médecine (SCMU) author Meister Isabel 968890 Section des sciences pharmaceutiques (FARMA) author Scapozza Leonardo 600318 Section des sciences pharmaceutiques (FARMA) author Vadas Oscar 0000-0003-3511-6479 508966 Département de microbiologie et médecine moléculaire (MIMOL) author Soldati-Favre Dominique 0000-0003-4156-2109 135114 Département de microbiologie et médecine moléculaire (MIMOL) e1013886 10.1371/journal.ppat.1013886 41604433 1553-7366 PMC12871999 https://dx.plos.org/10.1371/journal.ppat.1013886 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 Toxoplasma gondii 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 Toxoplasma gondii 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 Plasmodium falciparum 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 P. falciparum 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 Toxoplasma gondii and likely other Apicomplexa. Animals Cell Membrane / metabolism Cytokinesis / physiology Humans Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism Phylogeny Protozoan Proteins / genetics Protozoan Proteins / metabolism Toxoplasma / genetics Toxoplasma / metabolism Toxoplasma / pathogenicity Toxoplasma / physiology Toxoplasmosis / metabolism Toxoplasmosis / parasitology Dewey 615 Dewey 616 Dewey 590 Hôpitaux Universitaires de Genève HUG RC09-18 Swiss National Science Foundation Infiltrating the vital metabolite transportome of the vestigal plastid of Apicomplexa 216166 CH 54 Département de microbiologie et médecine moléculaire 21B 31 Section des sciences pharmaceutiques 17 23 Institut de génétique et de génomique 0DH false 443 Biologie d'un parasite intracellulaire obligatoire 773 880 Biochimie pharmaceutique PLOS pathogens 22 1 c3d14f43-c560-4216-9cea-21559a50bda3 Article (Published version) Public journal.ppat.1013886-3.pdf 4355786 application/pdf CC BY-4.0 75ea737906ef807f34de3e97d79a753290adb0522b2c6369835ad6a2017f4ad3 bcbc772f-7a0e-472a-8764-10b93e096ff1 Supplemental data Public 10_1371_journal_ppat_1013886.zip 10897618 application/zip 9f05b0e24c33a55584fbe137548dc2d080cdd6f7f6c3b88cdb9732d41e319f57 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté des sciences / Section des sciences pharmaceutiques Centres et instituts / Institut de génétique et de génomique

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A Spinster-like Transporter at the Inner Membrane Complex is critical for Toxoplasma gondii cytokinesis, motility and invasion	PLOS pathogens	2026	32	19
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