Stage-Dependent Expression and Vacuolar Localization of lasmodium berghei Chloroquine Resistance Transporter (CRT).

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology Pub Date : 2025-10-10 DOI:10.1016/j.molbiopara.2025.111703

Francois Korbmacher, Manuel Rauch, Sanketha Kenthirapalan, Taco W A Kooij, Alexander G Maier, Kai Matuschewski

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引用次数: 0

Abstract

Plasmodium parasites encode a chloroquine resistance transporter (CRT), which is an integral membrane protein of the digestive vacuole and transports the antimalarial compound chloroquine out of this organelle. Here, we profiled the spatio-temporal expression of CRT during life cycle progression employing CRT-mCherry Plasmodium berghei parasites. We show that CRT is expressed during asexual blood stage growth and localizes to the hemozoin-containing digestive vacuole. The compartmentalized CRT-mCherry signal is also abundant in gametocytes and ookinetes, indicating that CRT continues to exert important functions in this digestive organelle up until mosquito midgut colonization. Expression is switched off during sporogony and early liver infection but CRT-mCherry is present again in mature liver stages, likely in preparation for blood infection. Together, visualization of the P. berghei digestive vacuole by endogenous tagging of PbCRT revealed expression of this transport protein and the presence of this cellular compartment beyond asexual propagation inside erythrocytes.

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伯氏疟原虫氯喹耐药转运体（CRT）的分期依赖性表达和液泡定位。

疟原虫编码一个氯喹耐药转运体（CRT），它是消化液泡的一种整体膜蛋白，并将抗疟化合物氯喹从这个细胞器中转运出去。在这里，我们利用CRT- mcherry疟原虫berghei寄生虫分析了CRT在生命周期进程中的时空表达。我们发现CRT在无性血期生长期间表达，并定位于含血色素的消化液泡。区隔化的CRT- mcherry信号在配子体和卵母细胞中也很丰富，表明CRT在蚊子中肠定植之前继续在这种消化细胞器中发挥重要作用。在孢子形成和早期肝脏感染期间表达被关闭，但在肝脏成熟阶段再次出现CRT-mCherry，可能是为血液感染做准备。同时，通过内源性PbCRT标记的伯氏假体消化液泡可视化显示了该转运蛋白的表达以及红细胞内无性繁殖之外的细胞室的存在。

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来源期刊

Molecular and biochemical parasitology 医学-寄生虫学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

63 days

期刊介绍： The journal provides a medium for rapid publication of investigations of the molecular biology and biochemistry of parasitic protozoa and helminths and their interactions with both the definitive and intermediate host. The main subject areas covered are: • the structure, biosynthesis, degradation, properties and function of DNA, RNA, proteins, lipids, carbohydrates and small molecular-weight substances • intermediary metabolism and bioenergetics • drug target characterization and the mode of action of antiparasitic drugs • molecular and biochemical aspects of membrane structure and function • host-parasite relationships that focus on the parasite, particularly as related to specific parasite molecules. • analysis of genes and genome structure, function and expression • analysis of variation in parasite populations relevant to genetic exchange, pathogenesis, drug and vaccine target characterization, and drug resistance. • parasite protein trafficking, organelle biogenesis, and cellular structure especially with reference to the roles of specific molecules • parasite programmed cell death, development, and cell division at the molecular level.