Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii.
Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii.
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蛋白激酶TgCDPK7调节弓形虫囊泡运输和磷脂合成
DOI：
10.1371/journal.ppat.1009325
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发表时间：
2021-03
期刊：
影响因子：
6.7
通讯作者：
Sharma P
中科院分区：
文献类型：
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作者：
Bansal P;Antil N;Kumar M;Yamaryo-Botté Y;Rawat RS;Pinto S;Datta KK;Katris NJ;Botté CY;Prasad TSK;Sharma P
顶复门寄生虫是人类主要疾病的病原体。钙依赖性蛋白激酶（CDPKs）是顶复门寄生虫细胞内发育的关键组分，因此被认为是有吸引力的药物靶标。CDPK7是该家族的非典型成员，其初步表征表明对顶复体恶性疟原虫和刚地弓形虫的细胞内发育至关重要。然而，它调节寄生虫复制的机制仍然未知。我们进行了T.缺乏TgCDPK7的弓形虫以鉴定其寄生靶标。我们的分析导致几个推定的TgCDPK7底物的鉴定涉及的关键过程，如磷脂（PL）的合成和囊泡贩运。引人注目的是，TgRab11a通过TgCDPK7磷酸化对寄生虫细胞内发育和蛋白质运输至关重要。脂质组学分析结合生化和细胞研究证实，TgCDPK7调节T.刚地。这些研究为TgCDPK7调节这些对寄生虫发育至关重要的过程提供了新的见解。在这项研究中，我们证明，蛋白激酶TgCDPK7调节细胞过程，如囊泡运输和磷脂的合成，这是至关重要的寄生虫弓形虫的发展。它通过在特定位点磷酸化来调节小的GTbR TgRab11a的定位，这对于重要的寄生虫蛋白的运输至关重要，并且对于寄生虫分裂也很重要。TgCDPK7可能调节参与磷脂酰乙醇胺生物合成的关键酶，这可能有助于这种重要磷脂的合成。这些和其他研究揭示了一种新的信号通路在顶复门寄生虫弓形虫。
Apicomplexan parasites are causative agents of major human diseases. Calcium Dependent Protein Kinases (CDPKs) are crucial components for the intracellular development of apicomplexan parasites and are thus considered attractive drug targets. CDPK7 is an atypical member of this family, which initial characterization suggested to be critical for intracellular development of both Apicomplexa Plasmodium falciparum and Toxoplasma gondii. However, the mechanisms via which it regulates parasite replication have remained unknown. We performed quantitative phosphoproteomics of T. gondii lacking TgCDPK7 to identify its parasitic targets. Our analysis lead to the identification of several putative TgCDPK7 substrates implicated in critical processes like phospholipid (PL) synthesis and vesicular trafficking. Strikingly, phosphorylation of TgRab11a via TgCDPK7 was critical for parasite intracellular development and protein trafficking. Lipidomic analysis combined with biochemical and cellular studies confirmed that TgCDPK7 regulates phosphatidylethanolamine (PE) levels in T. gondii. These studies provide novel insights into the regulation of these processes that are critical for parasite development by TgCDPK7. In this study, we demonstrate that protein kinase TgCDPK7 regulates cellular processes like vesicular trafficking and the synthesis of phospholipids, which are critical for the development of the parasite Toxoplasma gondii. It regulates the localization of a small GTPase TgRab11a by phosphorylating it at a specific site, which is critical for trafficking of important parasite proteins and is important for parasite division. TgCDPK7 may regulate key enzymes involved biogenesis of phosphatidylethanolamine, which may contribute to the synthesis of this important phospholipid. These and other studies shed light on a novel signaling pathway in apicomplexan parasite Toxoplasma gondii.
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通讯作者：
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