The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission.
The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission.
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DOI：
10.1038/s41598-018-33236-x
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发表时间：
2018-10-08
影响因子：
4.6
通讯作者：
Khan SM
中科院分区：
文献类型：
--
作者：
Marin-Mogollon C;van de Vegte-Bolmer M;van Gemert GJ;van Pul FJA;Ramesar J;Othman AS;Kroeze H;Miao J;Cui L;Williamson KC;Sauerwein RW;Janse CJ;Khan SM
P48/45和P230是6-半胱氨酸（6-cys）蛋白家族的两个成员，对啮齿动物和人类疟原虫的配子生育力非常重要，并且是主要的传播阻断疫苗抗原。啮齿动物和人类寄生虫编码P230的一个片段，称为P230 p。虽然P230在雄性和雌性寄生虫中表达，但P230 p仅在雄性配子母细胞和配子中表达。在啮齿类疟疾寄生虫中，这种蛋白质在整个生命周期中都是稳定的;然而，它在恶性疟原虫中的功能尚不清楚。使用CRISPR/Cas9方法，我们破坏了编码Pfp 230 p的基因，导致恶性疟原虫突变体（PfΔ p230 p）缺乏P230 p表达。PfΔ p230 p突变体产生正常数量的雄性和雌性配子体，其保留P48/45和P230的表达。激活后，雄性PfΔ p230 p配子体发生外鞭毛形成雄配子。然而，雄配子不能附着在红细胞上，导致体外缺乏特征性的出丝中心。在缺乏P230 p的情况下，受精卵形成以及卵囊和子孢子发育在蚊子中强烈减少（>98%）。这些观察结果表明，P230 p，如P230和P48/45，在恶性疟原虫雄性生育力和合子形成中具有重要作用，并值得进一步研究作为潜在的传播阻断疫苗候选者。
Two members of 6-cysteine (6-cys) protein family, P48/45 and P230, are important for gamete fertility in rodent and human malaria parasites and are leading transmission blocking vaccine antigens. Rodent and human parasites encode a paralog of P230, called P230p. While P230 is expressed in male and female parasites, P230p is expressed only in male gametocytes and gametes. In rodent malaria parasites this protein is dispensable throughout the complete life-cycle; however, its function in P. falciparum is unknown. Using CRISPR/Cas9 methodology we disrupted the gene encoding Pfp230p resulting in P. falciparum mutants (PfΔp230p) lacking P230p expression. The PfΔp230p mutants produced normal numbers of male and female gametocytes, which retained expression of P48/45 and P230. Upon activation male PfΔp230p gametocytes undergo exflagellation and form male gametes. However, male gametes are unable to attach to red blood cells resulting in the absence of characteristic exflagellation centres in vitro. In the absence of P230p, zygote formation as well as oocyst and sporozoite development were strongly reduced (>98%) in mosquitoes. These observations demonstrate that P230p, like P230 and P48/45, has a vital role in P. falciparum male fertility and zygote formation and warrants further investigation as a potential transmission blocking vaccine candidate.
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影响因子：
3.7
作者：
Lin JW;Annoura T;Sajid M;Chevalley-Maurel S;Ramesar J;Klop O;Franke-Fayard BM;Janse CJ;Khan SM
通讯作者：
Khan SM
影响因子：
3.1
作者：
ROEFFEN, W;GEERAEDTS, F;SAUERWEIN, R
通讯作者：
SAUERWEIN, R
影响因子：
1.5
作者：
Saeed, Sadia;Carter, Victoria;Dessens, Johannes T.
通讯作者：
Dessens, Johannes T.
影响因子：
2.2
作者：
KUMAR, N
通讯作者：
KUMAR, N
DOI：
10.1126/science.1235264
发表时间：
2013-05-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Molina-Cruz A;Garver LS;Alabaster A;Bangiolo L;Haile A;Winikor J;Ortega C;van Schaijk BC;Sauerwein RW;Taylor-Salmon E;Barillas-Mury C
通讯作者：
Barillas-Mury C