An ancient protein phosphatase, SHLP1, is critical to microneme development in Plasmodium ookinetes and parasite transmission.
An ancient protein phosphatase, SHLP1, is critical to microneme development in Plasmodium ookinetes and parasite transmission.
复制标题
DOI：
10.1016/j.celrep.2013.01.032
复制
发表时间：
2013-03-28
期刊：
影响因子：
8.8
通讯作者：
Tewari R
中科院分区：
文献类型：
--
作者：
Patzewitz EM;Guttery DS;Poulin B;Ramakrishnan C;Ferguson DJ;Wall RJ;Brady D;Holder AA;Szöőr B;Tewari R
在疟疾寄生虫中，由可逆的蛋白磷酸化(由激酶和磷酸酶催化)控制的信号通路对于增进对寄生虫生物学的了解和识别新的药物靶点都是非常感兴趣的。在这里，我们报告了一种古老的细菌类希瓦纳氏菌蛋白磷酸酶(SHLP1)在疟原虫中的功能分析，该酶仅在细菌、真菌、原生生物和植物中发现。SHLP1在无性血液期中大量表达，在寄生虫生命周期的所有阶段都有表达。SHLP1缺失导致卵母细胞(受精卵)发育减少，微线体形成，卵囊形成完全消融，从而阻断寄生虫的传播。这种缺陷是由雌配子携带的，可以通过将突变的动子直接注射到蚊子的血腔中来拯救，那里会形成卵囊。本研究强调了SHLP1在运动疟原虫生物学中的多种功能，并提示其可能成为阻断寄生虫传播的新的药物靶点。►SHLP1具有对磷酸蛋白磷酸酶抑制剂不敏感的磷酸酶活性，►SHLP1缺失导致动细胞和微线体发育减少，►SHLP1是由雌配子►SHLP1缺失导致卵囊切除，对寄生虫传播起关键作用的蛋白(由蛋白激酶和磷酸酶催化)在疟原虫中引起了极大的兴趣。在这里，Tewari和他的同事报告了首次对啮齿动物疟原虫中的希瓦尼拉样蛋白磷酸酶(SHLP1)进行的功能分析。SHLP1是一种酶，以前只在细菌、真菌、原生生物和植物中报道过。该基因的缺失会导致受精卵(动子)的发育减少，以及与侵入蚊子肠道相关的细胞器(微线虫)的破坏，从而导致寄生虫传播的完全消融。
Signaling pathways controlled by reversible protein phosphorylation (catalyzed by kinases and phosphatases) in the malaria parasite Plasmodium are of great interest, for both increased understanding of parasite biology and identification of novel drug targets. Here, we report a functional analysis in Plasmodium of an ancient bacterial Shewanella-like protein phosphatase (SHLP1) found only in bacteria, fungi, protists, and plants. SHLP1 is abundant in asexual blood stages and expressed at all stages of the parasite life cycle. shlp1 deletion results in a reduction in ookinete (zygote) development, microneme formation, and complete ablation of oocyst formation, thereby blocking parasite transmission. This defect is carried by the female gamete and can be rescued by direct injection of mutant ookinetes into the mosquito hemocoel, where oocysts develop. This study emphasizes the varied functions of SHLP1 in Plasmodium ookinete biology and suggests that it could be a novel drug target for blocking parasite transmission. ► SHLP1 has phosphatase activity insensitive to phosphoprotein phosphatase inhibitors ► SHLP1 deletion results in reduced ookinete and microneme development ► SHLP1 is contributed by the female gamete ► SHLP1 deletion results in oocyst ablation and is critical for parasite transmission Reversible protein phosphorylation (catalyzed by protein kinases and phosphatases) in the malaria parasite Plasmodium is of great interest. Here, Tewari and colleagues report the first functional analysis of a Shewanella-like protein phosphatase (SHLP1) in rodent Plasmodium. SHLP1 is an enzyme that was reported previously only in bacteria, fungi, protists, and plants. Deletion of the gene results in reduced development of zygotes (ookinetes) and disruption of organelles (micronemes) associated with invasion into the mosquito gut, thus resulting in complete ablation of parasite transmission.
登录
查看更多内容
影响因子：
3.6
作者：
Ecker A;Bushell ES;Tewari R;Sinden RE
通讯作者：
Sinden RE
疟原虫中具有 kelch 样结构域 (PPKL) 的独特蛋白磷酸酶可调节动动体分化、运动和侵袭。
影响因子：
6.7
作者：
Guttery DS;Poulin B;Ferguson DJ;Szöőr B;Wickstead B;Carroll PL;Ramakrishnan C;Brady D;Patzewitz EM;Straschil U;Solyakov L;Green JL;Sinden RE;Tobin AB;Holder AA;Tewari R
通讯作者：
Tewari R
伯氏疟原虫 CTRP 基因的靶向破坏揭示了其在媒介蚊子疟疾感染中的重要作用。
影响因子：
15.3
作者：
Yuda, M;Sakaida, H;Chinzei, Y
通讯作者：
Chinzei, Y
影响因子：
6.7
作者：
Moon RW;Taylor CJ;Bex C;Schepers R;Goulding D;Janse CJ;Waters AP;Baker DA;Billker O
通讯作者：
Billker O
影响因子：
3.4
作者：
Andreeva AV;Kutuzov MA
通讯作者：
Kutuzov MA