A Putative Small Solute Transporter Is Responsible for the Secretion of G377 and TRAP-Containing Secretory Vesicles during <i>Plasmodium</i> Gamete Egress and Sporozoite Motility

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.调控性蛋白分泌对于疟原虫（malaria parasite）的生命周期推进以及哺乳类宿主与蚊媒之间的传播至关重要。在从宿主向蚊媒传播的过程中，嗜锇体（osmiophilic bodies）这类高度特化的分泌囊泡的胞吐作用，是溶解红细胞与纳虫泡膜以实现配子逸出的关键步骤。将TRAP家族（TRAP family）黏附蛋白从微线体（micronemes）定位至子孢子（sporozoite）表面，对于疟原虫的滑行运动以及蚊媒向哺乳类宿主的传播不可或缺。本研究在伯氏疟原虫（Plasmodium berghei）中发现，推定泛酸转运体PAT在配子体与子孢子内两类不同囊泡的融合过程中发挥保守功能。PAT是配子体内嗜锇体以及子孢子内微线体的膜组分。尽管激活后嗜锇体的形成与向细胞表面的转运均正常，但PAT缺陷型配子无法释放其内容物，仍滞留于红细胞内，无法完成受精以及在蚊体内的进一步发育。缺失PAT的子孢子无法分泌TRAP蛋白，丧失运动能力，因此无法感染后续的啮齿类宿主。综上，伯氏疟原虫PAT似乎并非在寄生虫传播过程中充当泛酸转运体，而是在两个不同生命周期阶段的两类不同囊泡群体中调控胞吐作用。