Digestive vacuole biogenesis in the malaria parasite

疟疾寄生虫的消化液泡生物发生

基本信息

批准号：
7236650
负责人：
Marcus C Lee
金额：
$ 5.8万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-20 至 2008-07-19
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7236650
关键词：
4-aminoquinoline Ablation Address Amino Acids Antimalarials Applied Genetics Biogenesis Biological Assay Catabolism Cell membrane Cells Chemicals Chloroquine Chloroquine resistance Cytosol Defect Development Disruption Drug Metabolic Detoxication Dynamin Endocytosis Endopeptidases Erythrocytes Event Family Fellowship Fluorescence Microscopy Genes Genetic Genome Heme Hemoglobin Human Individual Infection Ingestion Intracellular Transport Malaria Mediating Membrane Membrane Proteins Methods Names Organelles Orthologous Gene Oxidative Stress Parasites Pathway interactions Peptide Hydrolases Physiologic pulse Plasmodium Plasmodium falciparum Point Mutation Protein Secretion Proteins Pulse taking Quinine Role Route Site Sorting - Cell Movement Staging Superoxide Dismutase Testing Vacuolar Protein Sorting Vacuole Yeasts chemical genetics chemotherapy histidine-rich proteins insight intracellular protein transport loss of function plasmepsin protein transport research study trafficking uptake yeast protein

项目摘要

DESCRIPTION (provided by applicant): This application aims to understand the biogenesis of the digestive vacuole (DV) of the malaria parasite, Plasmodium falciparum. This acidic, lysosomal-like organelle is responsible for the degradation of large quantities of hemoglobin ingested from the host erythrocyte. The DV is also the site of action of the largest and historically the most clinically useful family of antimalarial drugs, the 4-aminoquinolines. Despite the importance of this organelle to parasite development and antimalarial chemotherapy, little is currently known about how both biosynthetic parasite proteins and components of the host cell cytosol are delivered to the DV during the intraerythrocytic lifecycle. I propose to determine which trafficking steps are essential for the transport of parasite and host cell proteins to the DV by genetic and chemical disruption of defined stages of intracellular transport. These studies will enable us to address the hypothesis that one pathway of parasite protein trafficking to the DV relies upon the Sec and Vps components of protein secretion and sorting. Our second major hypothesis is that uptake of hemoglobin and some host erythrocyte cytosol components proceeds via dynamin-dependent endocytosis.

描述（由申请人提供）：此申请旨在了解疟原虫寄生虫疟原虫恶性疟原虫的消化液泡（DV）的生物发生。这种酸性的溶酶体样细胞器是导致从宿主红细胞摄入的大量血红蛋白降解的原因。 DV也是最大和历史上最有用的抗疟药（4-氨基喹啉）家族的作用位置。尽管这种细胞器对寄生虫发育和抗疟疾化疗的重要性，但目前对宿主细胞质的生物合成寄生虫蛋白和宿主细胞质的成分均未众所周知，在炎症性细胞内生命周期期间将其递送到DV。我建议通过遗传和化学破坏细胞内转运的遗传和化学破坏，确定哪些运输步骤对于将寄生虫和宿主细胞蛋白运输至DV至关重要。这些研究将使我们能够解决以下假设：寄生虫蛋白运输到DV的一种途径依赖于蛋白质分泌和分类的SEC和VPS成分。我们的第二个主要假设是，血红蛋白和某些宿主红细胞细胞胞质成分的摄取是通过动力蛋白依赖性内吞作用进行的。