Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, UK.
Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, AB, T6G 2R3, Canada.
Nat Commun. 2023 Apr 15;14(1):2167. doi: 10.1038/s41467-023-37431-x.
Apicomplexan parasites have immense impacts on humanity, but their basic cellular processes are often poorly understood. Where endocytosis occurs in these cells, how conserved this process is with other eukaryotes, and what the functions of endocytosis are across this phylum are major unanswered questions. Using the apicomplexan model Toxoplasma, we identified the molecular composition and behavior of unusual, fixed endocytic structures. Here, stable complexes of endocytic proteins differ markedly from the dynamic assembly/disassembly of these machineries in other eukaryotes. We identify that these endocytic structures correspond to the 'micropore' that has been observed throughout the Apicomplexa. Moreover, conserved molecular adaptation of this structure is seen in apicomplexans including the kelch-domain protein K13 that is central to malarial drug-resistance. We determine that a dominant function of endocytosis in Toxoplasma is plasma membrane homeostasis, rather than parasite nutrition, and that these specialized endocytic structures originated early in infrakingdom Alveolata likely in response to the complex cell pellicle that defines this medically and ecologically important ancient eukaryotic lineage.
顶复门寄生虫对人类有巨大影响，但它们的基本细胞过程往往了解甚少。这些细胞中内吞作用发生的位置、该过程在其他真核生物中保守程度如何以及内吞作用在该门中的功能是什么，这些都是尚未解决的主要问题。我们使用顶复门模型弓形虫来鉴定不寻常的、固定的内吞结构的分子组成和行为。在这里，内吞蛋白的稳定复合物与其他真核生物中这些机制的动态组装/拆卸明显不同。我们发现这些内吞结构与在整个顶复门中观察到的“微孔”相对应。此外，在包括kelch 结构域蛋白 K13 的顶复门生物中，都能看到这种结构的保守分子适应性，K13 是疟疾药物耐药性的关键。我们确定，在弓形虫中，内吞作用的主要功能是质膜稳态，而不是寄生虫营养，这些专门的内吞结构起源于早期的真核生物亚界纤毛门，可能是为了应对定义这一具有医学和生态学重要性的古老真核生物谱系的复杂细胞被膜。
