Centre de recherche en infectiologie du CHU de Québec-Université Laval, Quebec City, Quebec, Canada.
Sci Rep. 2017 Oct 5;7(1):12710. doi: 10.1038/s41598-017-12762-0.
Despite marked reductions in morbidity and mortality in the last ten years, malaria still takes a tremendous toll on human populations throughout tropical and sub-tropical regions of the world. The absence of an effective vaccine and resistance to most antimalarial drugs available demonstrate the urgent need for new intervention strategies. Phosphoinositides are a class of lipids with critical roles in numerous processes and their specific subcellular distribution, generated through the action of kinases and phosphatases, define organelle identity in a wide range of eukaryotic cells. Recent studies have highlighted important functions of phosphoinositide kinases in several parts of the Plasmodium lifecycle such as hemoglobin endocytosis and cytokinesis during the erythrocytic stage however, nothing is known with regards to the parasite's putative phosphoinositide phosphatases. We present the identification and initial characterization of a putative homologue of the SAC1 phosphoinositide phosphatase family. Our results show that the protein is expressed throughout the asexual blood stages and that it localises to the endoplasmic reticulum and potentially to the Golgi apparatus. Furthermore, conditional knockdown and knockout studies suggest that a minimal amount of the protein are likely required for survival during the erythrocytic cycle.
尽管在过去十年中发病率和死亡率显著下降，但疟疾仍然在世界上热带和亚热带地区的人类中造成了巨大的损失。缺乏有效的疫苗和对大多数现有抗疟药物的耐药性表明，迫切需要新的干预策略。磷酸肌醇是一类在许多过程中具有关键作用的脂质，其特定的亚细胞分布是通过激酶和磷酸酶的作用产生的，这定义了广泛的真核细胞中的细胞器身份。最近的研究强调了磷酸肌醇激酶在疟原虫生命周期的几个部分中的重要功能，例如在红细胞阶段的血红蛋白内吞作用和胞质分裂，但是对于寄生虫的假定磷酸肌醇磷酸酶却一无所知。我们介绍了 SAC1 磷酸肌醇磷酸酶家族的假定同源物的鉴定和初步特征。我们的结果表明，该蛋白在无性血阶段表达，并定位于内质网，可能还有高尔基体。此外，条件性敲低和敲除研究表明，在红细胞周期中，可能需要少量的蛋白质才能存活。
