Intracellular Plasmodium aquaporin 2 is important for sporozoite production in the mosquito vector and malaria transmission.
Intracellular Plasmodium aquaporin 2 is important for sporozoite production in the mosquito vector and malaria transmission.
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DOI：
10.1073/pnas.2304339120
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发表时间：
2023-10-31
影响因子：
11.1
通讯作者：
Vlachou, Dina
中科院分区：
文献类型：
--
作者：
Bailey, Alexander J.;Ukegbu, Chiamaka Valerie;Giorgalli, Maria;Besson, Tanguy Rene Balthazar;Christophides, George K.;Vlachou, Dina
这里报道的结果揭示了疟疾寄生虫中独特进化的水通道蛋白，这对寄生虫生命周期的蚊子阶段子孢子的产生很重要。子孢子是蚊子叮咬后负责将疟疾传播给人类的寄生虫形式。水通道蛋白是已知的水和其他分子跨生物膜的转运蛋白。水通道蛋白具有不寻常的结构特征，并栖息在寄生虫细胞内的囊泡样细胞器中。由于水通道蛋白可以被药物靶向，我们建议这种水通道蛋白可能是未来抗疟干预的一个有前途的目标。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被视为潜在干预目标的蛋白质家族，它是促进水和其他溶质跨膜运动的通道。我们确定了一个水通道蛋白在疟疾寄生虫，并证明它是重要的完成疟原虫发展的蚊子载体。人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上建立的卵囊内的子孢子产生，极大地限制了唾液腺的寄生虫感染和向新宿主的传播。在伯氏疟原虫中AQP 2的体内表位标记，结合免疫荧光测定，揭示了该蛋白定位于配子体、动合子和子孢子的细胞质中发现的囊泡样细胞器中。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，这表明它们可能是动态内膜系统的一部分。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，与细胞内水通道蛋白最为相似。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，在已知的水通道蛋白。这与AQP 2对疟疾传播的重要性相结合，表明AQP 2可能是抗疟干预措施的一个富有成效的目标。
The results reported here uncover a uniquely evolved aquaporin in malaria parasites, which is important for production of sporozoites during the mosquito phase of the parasite lifecycle. Sporozoites are the parasite form responsible for malaria transmission to humans following a mosquito bite. Aquaporins are known transporters of water and other molecules across biological membranes. The aquaporin has unusual structural features and inhabits a vesicle-like organelle inside parasite cells. Since aquaporins can be targeted by drugs, we propose that this aquaporin may be a promising target of future antimalarial interventions. 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 an aquaporin in malaria parasites and demonstrate that it is important for completion of Plasmodium development in the mosquito vector. Disruption of AQP2 in the human parasite Plasmodium falciparum and the rodent parasite Plasmodium berghei blocks sporozoite production inside oocysts established on mosquito midguts, greatly limiting parasite infection of salivary glands and transmission to a new host. In vivo epitope tagging of AQP2 in P. berghei, combined with immunofluorescence assays, reveals that the protein is localized in vesicle-like 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 endomembrane system. Phylogenetic analysis confirms that AQP2 is unique to malaria and closely related parasites and most closely resembles 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 among known aquaporins. This in conjunction with the importance of AQP2 for malaria transmission suggests that AQP2 may be a fruitful target of 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
影响因子：
11.4
作者：
Bestetti, Stefano;Galli, Mauro;Medrano-Fernandez, Iria
通讯作者：
Medrano-Fernandez, Iria
影响因子：
4.1
作者：
Bienert, Gerd P.;Cavez, Damien;Chaumont, Francois
通讯作者：
Chaumont, Francois
DOI：
10.3390/life11020084
发表时间：
2021-01-25
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
McGovern OL;Rivera-Cuevas Y;Carruthers VB
通讯作者：
Carruthers VB
影响因子：
5.3
作者：
Morishita, Y;Matsuzaki, T;Ishibashi, K
通讯作者：
Ishibashi, K