The Toxoplasma micropore mediates endocytosis for selective nutrient salvage from host cell compartments

Wan, W; Dong, H; Lai, D; Yang, J; He, K; Tang, X; Liu, Q; Hide, G; Zhu, X; Sibley, L; Lun, Z; Long, S

Abstract

Apicomplexan parasite growth and replication relies on nutrient acquisition from host cells, in which intracellular multiplication occurs, yet the mechanisms that underlie the nutrient salvage remain elusive. Numerous ultrastructural studies have documented a plasma membrane invagination with a dense neck, termed the micropore, on the surface of intracellular parasites. However, the function of this structure remains unknown. Here we validate the micropore as an essential organelle for endocytosis of nutrients from the host cell cytosol and Golgi in the model apicomplexan Toxoplasma gondii. Detailed analyses demonstrated that Kelch13 is localized at the dense neck of the organelle and functions as a protein hub at the micropore for endocytic uptake. Intriguingly, maximal activity of the micropore requires the ceramide de novo synthesis pathway in the parasite. Thus, this study provides insights into the machinery underlying acquisition of host cell-derived nutrients by apicomplexan parasites that are otherwise sequestered from host cell compartments.

Citation

Wan, W., Dong, H., Lai, D., Yang, J., He, K., Tang, X., …Long, S. (in press). The Toxoplasma micropore mediates endocytosis for selective nutrient salvage from host cell compartments. Nature communications, 14(1), 997. https://doi.org/10.1038/s41467-023-36571-4

• Journal Article Type: Article
• Acceptance Date: Feb 3, 2023
• Online Publication Date: Feb 22, 2023
• Deposit Date: Mar 28, 2023
• Publicly Available Date: Mar 28, 2023
• Journal: Nature Communications
• Print ISSN: 2041-1723
• Volume: 14
• Issue: 1
• Pages: 997
• DOI: https://doi.org/10.1038/s41467-023-36571-4
• Keywords: Parasite biology, Parasite physiology, Parasite host response
• Publisher URL: https://doi.org/10.1038/s41467-023-36571-4
• Additional Information: Funders : National Natural Science Foundation of China;National Key Research and Development Program of China;Fund for Shanxi “1331 Project”;National Key Laboratory of Veterinary Public Health Security and School of Veterinary Medicine, China Agricultural University, 100193, Beijing, China; Projects : The Toxoplasma micropore mediates endocytosis for selective nutrient salvage from host cell compartments; Grant Number: 31873009; Grant Number: 31772445; Grant Number: 2021YFC2300802; Grant Number: 20211331-13; Grant Number: Start up package