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

Wenyan Wan, Hui Dong, Lai De-Hua, Jiong Yang, Kai He, Xiaoyan Tang, Qun Liu, Geoff Hide, Xing-Quan Zhu, L. David Sibley, Zhao-Rong Lun and Shaojun Long ()
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Wenyan Wan: China Agricultural University
Hui Dong: China Agricultural University
Lai De-Hua: School of Life Sciences, Sun Yat-Sen University
Jiong Yang: School of Life Sciences, Sun Yat-Sen University
Kai He: China Agricultural University
Xiaoyan Tang: China Agricultural University
Qun Liu: China Agricultural University
Geoff Hide: School of Science, Engineering and Environment, University of Salford
Xing-Quan Zhu: Shanxi Agricultural University
L. David Sibley: Washington University School of Medicine in Saint Louis
Zhao-Rong Lun: School of Life Sciences, Sun Yat-Sen University
Shaojun Long: China Agricultural University

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36571-4

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