ER-shaping proteins of Plasmodium

摘要 真核细胞的内质网是一种重要的细胞器，具有多种重要功能 包括蛋白质分泌。它的功能与它的形态密切相关。高等真核生物的研究表明 产生ER管状网络所需的关键蛋白质的突变会导致特定的生长和 发育缺陷。与高等真核生物相比，人们对内质网在早期是如何形成的知之甚少 真核生物，如原生动物。 内质网结构在原生动物寄生虫中，疟原虫是动态的和阶段特定的，但其分子 决定因素是未知的。为了了解内质网如何在疟原虫的不同阶段获得其形状， 我们鉴定了关键的内质网形成蛋白的同源蛋白，包括那些包含网状同源结构域的蛋白。 这些蛋白质中的一种在体外诱导细胞膜弯曲。缺乏这种蛋白质的伯氏疟原虫有 畸形内质网是一种扩大的消化液泡，在无性周期中严重减弱，但会感染 正常情况下是肝细胞。我们假设我们确定的可能的疟原虫ER-Shape蛋白具有 在维持适当的内质网结构/功能方面发挥特定阶段的作用。这项提案将决定捐款 这些蛋白质在形成红细胞期和肝期疟原虫ER中的作用，使用形态和 伯氏假单胞菌基因敲除的超微结构研究。它将确定他们的损失对关键ER的影响 功能，蛋白质在寄生虫中的运输。我们的研究将提供ER架构、 蛋白质贩运和疟疾寄生虫在不同宿主环境中居住的能力。

ABSTRACT The endoplasmic reticulum (ER) of eukaryotic cells is an essential organelle with many critical functions including, protein secretion. Its function is closely tied to its morphology. Work in higher eukaryotes has shown that mutations in key proteins required to generate the ER tubular network cause specific growth and developmental defects. In contrast to higher eukaryotes, little is known of how the ER is shaped in early eukaryotes such as protozoa. ER structure in the protozoan parasite, Plasmodium is dynamic and stage-specific but its molecular determinants are unknown. To understand how the ER acquires its shape in different stages of Plasmodium, we identified homologs of key ER-shaping proteins including ones that contain a reticulon homology domain. One of these protein induces membrane curvature in vitro. P. berghei parasites lacking the protein have dysmorphic ER, an enlarged digestive vacuole, are severely attenuated in the asexual cycle but infect hepatocytes normally. We hypothesize that the putative Plasmodium ER-shaping proteins we identified have stage-specific roles in maintaining proper ER structure/function. This proposal will determine the contributions of these proteins in shaping the ER of erythrocytic and hepatic stages of Plasmodium, using morphological and ultrastructural studies of P. berghei gene-knockouts. It will determine the effect of their loss on a key ER function, protein trafficking in the parasite. Our study will provide the first causal link between ER architecture, protein trafficking and the ability of the malaria parasite to reside in different host environments.