Identification of a subtelomeric gene family expressed during the asexual-sexual stage transition in Plasmodium falciparum
Identification of a subtelomeric gene family expressed during the asexual-sexual stage transition in Plasmodium falciparum
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DOI：
10.1016/j.molbiopara.2005.05.010
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发表时间：
2005-09-01
影响因子：
1.5
通讯作者：
Williamson, KC
中科院分区：
文献类型：
--
作者：
Eksi, S;Haile, Y;Williamson, KC
为了传播疟疾，寄生虫必须经历性分化成为成熟的配子体。然而，寄生虫生命周期中这一关键转变的分子基础尚不清楚。Pfg14.744，Pfg14.745，Pfg14.748，Pfg14.763，Pfg14.752和Pfg6.6是一个36个基因的恶性疟原虫特异性亚端粒超家族的成员，被发现在寄生虫中表达，致力于性发育的Pfs16和Pfg27的共表达。北方印迹表明Pfg 14.744和Pfg 14.748在疟原虫分化为形态学上不同的配子体之前首先表达，转录持续增加，直到形成II期配子体，然后迅速减少。免疫荧光分析表明，这两种蛋白质只产生于环阶段的寄生虫，致力于配子体发生和本地化的寄生虫空泡（PV）（B）的早期环阶段的寄生虫的亚群。随着寄生虫的继续发育，Pfg14.748仍然存在于寄生虫空泡中，而在红细胞中检测到Pfg14.744。单独的任一基因的5'侧翼区足以驱动绿色荧光蛋白（GFP）的早期配子体特异性表达。在用含有Pfg14.748 5'侧翼区的质粒转染的寄生虫中，在观察到I期配子体之前的周期中，在少量的配子体中观察到荧光。这种表达模式与裂殖子释放和红细胞侵入之前的性分化承诺是一致的。进一步研究这些基因在从无性到性分化的转变中的作用，可以为阻断疟疾传播提供新的策略。(c)2005 Elsevier B.V.保留所有权利。
For malaria transmission, the parasite must undergo sexual differentiation into mature gametocytes. However, the molecular basis for this critical transition in the parasites life cycle is unknown. Six previously uncharacterized genes, Pfg14.744, Pfg14.745, Pfg14.748, Pfg14.763, Pfg14.752 and Pfg6.6 that are members of a 36 gene Plasmodium falciparum-specific subtelomeric superfamily were found to be expressed in parasites that are committed to sexual development as suggested by co-expression of Pfs16 and Pfg27. Northern blots demonstrated that Pfg14.744 and Pfg14.748 were first expressed before the parasites differentiated into morphologically distinct gametocytes, transcription continued to increase until stage II gametocytes were formed and then rapidly decreased. Immunofluorescence assays indicated that both proteins were only produced in the subpopulation of ring stage parasites that are committed to gametocytogenesis and both localized to the parasitophorous vacuole (PV)(b) of the early ring stage parasites. As the parasites continued to develop Pfg14.748 remained within the parasitophorous vacuole, while Pfg14.744 was detected in the erythrocyte. The 5' flanking region of either gene alone was sufficient to drive early gametocyte specific expression of green fluorescent protein (GFP). In parasites transfected with a plasmid containing the Pfg14.748 5' flanking region immediately upstream of GFP, fluorescence was observed in a small number of schizonts the cycle before stage I gametocytes were observed. This expression pattern is consistent with commitment to sexual differentiation prior to merozoite release and erythrocyte invasion. Further investigation into the role of these genes in the transition from asexual to sexual differentiation could provide new strategies to block malaria transmission. (c) 2005 Elsevier B.V. All rights reserved.