Digestive vacuole biogenesis in the malaria parasite

疟疾寄生虫的消化液泡生物发生

• 批准号: 7608571
• 负责人: Marcus C Lee
• 金额: $ 0.87万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 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/7608571
• 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

This proposal 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.

该提案旨在了解疟原虫消化泡（DV）的生物发生， 恶性疟原虫这种酸性的、溶酶体样的细胞器负责降解大的 从宿主红细胞摄取的血红蛋白量。DV也是最大的行动现场 历史上临床上最有用的抗疟药家族4-氨基喹啉。尽管 该细胞器对寄生虫发育和抗疟化疗的重要性，目前知之甚少 关于生物合成的寄生虫蛋白质和宿主细胞胞质溶胶的成分是如何被递送到 红细胞内生命周期中的DV。我建议确定哪些贩运步骤对于 通过遗传和化学破坏确定阶段的病毒， 胞内转运这些研究将使我们能够解决一个假设，即寄生虫的一个途径 蛋白质运输到DV依赖于蛋白质分泌和分选的Sec和Vps组分。我们 第二个主要假设是血红蛋白和某些宿主红细胞胞质溶胶成分的摄取 通过动力蛋白依赖性内吞作用进行。