Plasmodium berghei leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development.
Plasmodium berghei leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development.
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蛋白磷酸酶1（PP 1）是疟原虫发育的关键酶。然而，其调控的详细机制仍有待破译。在这里，我们报告了伯氏疟原虫富含亮氨酸的重复蛋白1（PbLRR 1），SDS 22，最古老和保守的PP 1相互作用的直向同源物的功能特性。我们的研究表明，PbLRR 1表达在红细胞内发育的寄生虫，并在蚊子的受精卵阶段。PbLRR 1在无性和有性阶段都可以与PbPP 1复合，并抑制其磷酸酶活性。遗传分析表明，PbLRR 1缺失对卵囊的发育产生不利影响。与磷酸蛋白质组学研究相关的PbLRR 1相互作用组分析确定了几种新的推定PbLRR 1/PbPP 1伙伴。其中一些伴侣以前被认为是寄生虫性发育所必需的。有趣的是，第一次，抑制剂3（I3），一个众所周知的和直接的相互作用的疟原虫PP 1，被发现显着低磷酸化的PbLRR 1耗尽的寄生虫。这些数据，沿着在LRR 1相互作用组中检测到I3与PP 1，强烈表明PbI 3的磷酸化状态受PP 1-LRR 1复合物的控制，并可能直接促进卵囊发育。这项研究提供了新的见解，以前未被识别的PbPP 1通过其与PbLRR 1的相互作用，疟原虫卵囊发育的精细调控。
Protein phosphatase 1 (PP1) is a key enzyme for Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. Here, we report the functional characterization of the Plasmodium berghei leucine-rich repeat protein 1 (PbLRR1), an orthologue of SDS22, one of the most ancient and conserved PP1 interactors. Our study shows that PbLRR1 is expressed during intra-erythrocytic development of the parasite, and up to the zygote stage in mosquitoes. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic analysis demonstrates that PbLRR1 depletion adversely affects the development of oocysts. PbLRR1 interactome analysis associated with phospho-proteomics studies identifies several novel putative PbLRR1/PbPP1 partners. Some of these partners have previously been characterized as essential for the parasite sexual development. Interestingly, and for the first time, Inhibitor 3 (I3), a well-known and direct interactant of Plasmodium PP1, was found to be drastically hypophosphorylated in PbLRR1-depleted parasites. These data, along with the detection of I3 with PP1 in the LRR1 interactome, strongly suggest that the phosphorylation status of PbI3 is under the control of the PP1–LRR1 complex and could contribute (in)directly to oocyst development. This study provides new insights into previously unrecognized PbPP1 fine regulation of Plasmodium oocyst development through its interaction with PbLRR1.
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影响因子：
7.3
作者：
Chen, Mark J.;Dixon, Jack E.;Manning, Gerard
通讯作者：
Manning, Gerard
影响因子：
3.6
作者：
Ecker A;Bushell ES;Tewari R;Sinden RE
通讯作者：
Sinden RE
DOI：
10.1046/j.1432-1327.1999.00344.x
发表时间：
1999-05-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Ceulemans, H;Van Eynde, A;Bollen, M
通讯作者：
Bollen, M
影响因子：
3
作者：
Caldelari，Reto;Dogga，Sunil;Heussler，Volker
通讯作者：
Heussler，Volker
影响因子：
3.4
作者：
Blisnick, T;Vincensini, L;Braun-Breton, C
通讯作者：
Braun-Breton, C