Intracellular Plasmodium aquaporin 2 is required for sporozoite production in the mosquito vector and malaria transmission
Intracellular Plasmodium aquaporin 2 is required for sporozoite production in the mosquito vector and malaria transmission
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细胞内疟原虫水通道蛋白 2 是蚊媒和疟疾传播中子孢子产生所必需的
DOI：
10.1101/2023.03.15.532816
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bailey A
中科院分区：
文献类型：
--
作者：
Bailey A
疟疾仍然是一种毁灭性疾病，由于目前的措施未能控制其传播，因此需要采取新的干预措施。水通道蛋白是一个长期以来一直作为潜在干预靶点的蛋白质家族，它是促进水和其他溶质跨膜运动的通道。我们在疟疾寄生虫中发现了一种新的水通道蛋白，并证明它对蚊子传播疾病至关重要。在人类寄生虫恶性疟原虫和啮齿动物寄生虫伯氏疟原虫中，AQP 2的破坏阻断了蚊子中肠卵囊内的子孢子产生，阻止了寄生虫对唾液腺的感染和传播到新宿主。berghei结合免疫荧光测定揭示了该蛋白定位于先前在配子母细胞、动合子和子孢子的细胞质中发现的未表征的细胞器中。这些细胞器的数量在个体寄生虫和生命周期阶段之间变化，表明它们可能是动态内溶酶体系统的一部分。系统发育分析证实，AQP 2是疟疾和密切相关的寄生虫所特有的，与其他细胞内水通道蛋白关系最密切。结构预测分析确定了几个不寻常的功能，包括一个大的辅助细胞外环和选择性过滤器中的丙氨酸-苯丙氨酸取代主要决定孔功能，一个独特的功能，没有发现在任何水通道蛋白研究的日期。这与疟疾传播对AQP 2的要求相结合，表明AQP 2可能是新型抗疟干预措施的一个富有成效的新靶点。
Malaria remains a devastating disease and, with current measures failing to control its transmission, there is a need for novel interventions. A family of proteins that have long been pursued as potential intervention targets are aquaporins which are channels facilitating the movement of water and other solutes across membranes. We identify a new aquaporin in malaria parasites and demonstrate that it is essential for disease transmission through mosquitoes. Disruption of AQP2 in the human parasitePlasmodium falciparumand the rodent parasitePlasmodium bergheiblocks sporozoite production inside oocysts established on mosquito midguts, preventing parasite infection of salivary glands and transmission to a new host.In vivoepitope tagging of AQP2 inP. berghei, combined with immunofluorescence assays, reveals that the protein is localized in previously uncharacterized organelles found in the cytoplasm of gametocytes, ookinetes and sporozoites. The number of these organelles varies between individual parasites and lifecycle stages suggesting that they are likely part of a dynamic endolysosomal system. Phylogenetic analysis confirms that AQP2 is unique to malaria and closely related parasites and most closely related to other intracellular aquaporins. Structure prediction analyses identify several unusual features, including a large accessory extracellular loop and an arginine-to-phenylalanine substitution in the selectivity filter principally determining pore function, a unique feature not found in any aquaporins studied to date. This in conjunction with the requirement of AQP2 for malaria transmission suggests that AQP2 may be a fruitful new target of novel antimalarial interventions.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
弓形虫中的单个水通道蛋白基因编码水/甘油/尿素促进剂，与植物液泡膜内在蛋白相似1
影响因子：
3.5
作者：
Slavica Pavlovic;J. Schultz;E. Beitz
通讯作者：
E. Beitz
DOI：
10.1101/2023.03.14.532540
发表时间：
2023-03
期刊：
bioRxiv
影响因子：
--
作者：
C. V. Ukegbu;A. R. Gomes;Maria Giorgalli;M. Campos;Alexander J Bailey;Tanguy Rene Balthazar Besson
通讯作者：
C. V. Ukegbu;A. R. Gomes;Maria Giorgalli;M. Campos;Alexander J Bailey;Tanguy Rene Balthazar Besson
影响因子：
5.3
作者：
Morishita, Y;Matsuzaki, T;Ishibashi, K
通讯作者：
Ishibashi, K
DOI：
10.1016/0035-9203(73)90031-x
发表时间：
1973-01-01
影响因子：
2.2
作者：
SINDEN, RE;GARNHAM, PCC
通讯作者：
GARNHAM, PCC