An ER-IMC bridge protein TgVPS13A and an IMC-resident scramblase TgDAT1 drive daughter budding in Toxoplasma gondii

PLOS Pathogens

卷:22

Research Article

Lin Zhao¹  Jiawen Fu¹  Swaroop Peddiraju²  Heming Chen¹  Keqin Huang¹  Ying Zhang¹  Nishith Gupta²  Qian Jiang¹  Honglin Jia¹ 

[1] State Key Laboratory of Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China

[2] Intracellular Parasite Education and Research Labs (iPEARL), Department of Biological Sciences, Birla Institute of Technology and Science, Pilani (BITS Pilani), Hyderabad, India

关键词: Lipids;    Toxoplasma gondii;    Biosynthesis;    Cell membranes;    Scramblase;    Endoplasmic reticulum;    Parasitic diseases;    Membrane proteins;   

DOI  :  10.1371/journal.ppat.1013865

 received in 2026-01-01, accepted in 2026-06-11,  发布年份 2026

来源: PLOS

【 摘 要 】

All alveolates including apicomplexan parasites contain an inner membrane complex (IMC) underneath the plasma membrane. The IMC is synthesized de novo during asexual replication (including endodyogeny, endopolygeny, and schizogony) and serves as a crucial scaffold for supporting cytoskeletal structures and the glideosome machinery for parasite locomotion. However, the mechanism(s) underlying the membrane biogenesis in the IMC are not well understood. Using a clinically-relevant and globally-prevalent pathogenic protist model, Toxoplasma gondii, we identified the TgVPS13A bridging the IMC to the endoplasmic reticulum (ER) – the major site of phospholipid synthesis. The multi-modular TgVPS13A plays a crucial role in the IMC biogenesis, functioning in concert with an ER-resident VAP protein (TgVAP) and a novel lipid scramblase (TgDAT1). TgDAT1 is recruited for the progeny formation sites during the early stages of budding. Conditional depletion of TgVPS13A, TgDAT1 or TgVAP results in collapse of the inner membrane complex, leading to parasite death, as visualized by endodyogeny-specific organelle markers. GFP-Lact-C2, a biosensor of phosphatidylserine and phosphatidylthreonine lipids made in the ER and enriched in the IMC, also mislocalizes upon protein depletion. In conclusion, we propose that TgVPS13A, together with TgVAP and TgDAT1, bridge the ER and IMC and mediate the inter-organelle transport of lipids, thus contributing to the organelle biogenesis and daughter budding in T. gondii.

【 授权许可】

CC BY   
Zhao et al 2026

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Figure 5. Mortar containing a fully ground sample (highlighted by red arrow), which has been concentrated by tilting

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