A Putative Small Solute Transporter Is Responsible for the Secretion of G377 and TRAP-Containing Secretory Vesicles during Plasmodium Gamete Egress and Sporozoite Motility.
A Putative Small Solute Transporter Is Responsible for the Secretion of G377 and TRAP-Containing Secretory Vesicles during Plasmodium Gamete Egress and Sporozoite Motility.
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DOI：
10.1371/journal.ppat.1005734
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发表时间：
2016-07
期刊：
影响因子：
6.7
通讯作者：
Mair GR
中科院分区：
文献类型：
--
作者：
Kehrer J;Singer M;Lemgruber L;Silva PA;Frischknecht F;Mair GR
调节的蛋白质分泌是疟原虫生命周期进展和哺乳动物宿主与蚊子载体之间传播所必需的。在从宿主到载体的传播过程中，高度特化的分泌囊泡（如嗜锇小体）的胞吐作用是红细胞和寄生虫空泡膜溶解的关键，从而使配子排出。TRAP家族粘附素从微丝到子孢子表面的定位对于寄生虫的滑行运动和从蚊子到哺乳动物宿主的传播是必不可少的。在这里，我们确定了一个保守的作用，为假定的泛酸转运蛋白PAT在伯氏疟原虫囊泡融合的两个不同类别的囊泡在配子体和子孢子。PAT是配子母细胞中嗜锇小体和子孢子中微丝的膜成分。尽管激活后嗜锇体正常形成并运输到细胞表面，但PAT缺陷的配子无法排出其内容物，保持在红细胞内，无法在蚊子体内受精和进一步发育。缺乏PAT的子孢子不能分泌TRAP，是不动的，因此不能感染随后的啮齿动物宿主。因此，伯氏疟原虫PAT似乎在两种不同的生命周期形式中调节两种不同的囊泡群体中的胞吐作用，而不是在寄生虫传播期间充当泛酸转运蛋白。疟疾寄生虫在蚊子和宿主之间的传播需要两个不同的生命周期阶段配子母细胞和子孢子。在这两种寄生虫形式中，传播依赖于阶段特异性囊泡的胞吐作用。在配子体中，这些囊泡释放蛋白质，允许从红细胞中排出和受精，因此需要在蚊子中建立感染。相反，蛋白质被分泌到子孢子的膜中，在那里它们在粘附和运动过程中发挥不同的作用，这两者对于传输回哺乳动物宿主至关重要。在这里，我们表明，寄生虫缺乏假定的小溶质转运蛋白PAT仍然能够形成囊泡在两种寄生虫的形式，但无法融合和分泌其内容。这导致寄生虫传入和传出蚊子的传播受损。我们的工作表明，一个单一的蛋白质可以调节功能不同类的囊泡在不同的生命周期形式的寄生虫的功能。
Regulated protein secretion is required for malaria parasite life cycle progression and transmission between the mammalian host and mosquito vector. During transmission from the host to the vector, exocytosis of highly specialised secretory vesicles, such as osmiophilic bodies, is key to the dissolution of the red blood cell and parasitophorous vacuole membranes enabling gamete egress. The positioning of adhesins from the TRAP family, from micronemes to the sporozoite surface, is essential for gliding motility of the parasite and transmission from mosquito to mammalian host. Here we identify a conserved role for the putative pantothenate transporter PAT in Plasmodium berghei in vesicle fusion of two distinct classes of vesicles in gametocytes and sporozoites. PAT is a membrane component of osmiophilic bodies in gametocytes and micronemes in sporozoites. Despite normal formation and trafficking of osmiophilic bodies to the cell surface upon activation, PAT-deficient gametes fail to discharge their contents, remain intraerythrocytic and unavailable for fertilisation and further development in the mosquito. Sporozoites lacking PAT fail to secrete TRAP, are immotile and thus unable to infect the subsequent rodent host. Thus, P. berghei PAT appears to regulate exocytosis in two distinct populations of vesicles in two different life cycle forms rather than acting as pantothenic transporter during parasite transmission. Transmission of the malaria parasite between mosquito and host requires two different life cycle stages—the gametocyte and the sporozoite. In both parasite forms, transmission is dependent on exocytosis of stage-specific vesicles. In gametocytes these vesicles release proteins allowing egress from red blood cells and fertilization, and are hence needed to establish an infection in the mosquito. In contrast, proteins are secreted into the membrane of the sporozoite, where they play distinct roles during adhesion and motility, both crucial for transmission back into the mammalian host. Here we show that parasites lacking the putative small solute transporter PAT are still able to form vesicles in both parasite forms but are unable to fuse and secrete their contents. This results in impaired parasite transmission into and from the mosquito. Our work shows that a single protein can regulate the function of functionally distinct classes of vesicles in different life cycle forms of a parasite.