Vesicle targeting in Plasmodium falciparum

恶性疟原虫中的囊泡靶向

基本信息

批准号：
7339641
负责人：
Julian Charles Rayner
金额：
$ 7.11万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7339641
关键词：
Address Apical Architecture Binding Binding Proteins Biochemical Biological Models Biology Blood Carrier Proteins Cell membrane Cells Cellular biology Cerebrum Cessation of life Chimera organism Cleaved cell Communities Cytosol Data Destinations Development Disputes Drug resistance Elements Endoplasmic Reticulum Epitopes Erythrocytes Eukaryota Eukaryotic Cell Fractionation Future Genome Goals Golgi Apparatus Health Hydrophobicity Immunoelectron Microscopy Immunofluorescence Immunologic Immunofluorescence Microscopy Intervention Knowledge Length Life Cycle Stages Ligands Location Malaria Maps Measures Mediating Membrane Molecular Nature Numbers Organelles Organism Parasites Pathogenesis Pathology Pathway interactions Personal Satisfaction Phosphorus Plasmodium falciparum Play Prevention Protein Export Pathway Protein Secretion Protein Sortings Public Health Race Research Rest Reverse Transcriptase Polymerase Chain Reaction Role SNAP receptor Saponin Saponins Signal Transduction Sorting - Cell Movement Specificity Staging Structure Surface Symptoms Techniques Testing Time Transport Vesicles Vesicle Work Yeasts base experience innovation knowledge base molecular array novel protein transport receptor soluble NSF attachment protein target SNARE proteins tool vesicular SNARE proteins

项目摘要

DESCRIPTION (provided by applicant): Plasmodium falciparum parasites cause over 1 million deaths from malaria each year and represent one of the most significant public health challenges facing the global community. The secretory pathway of blood- stage P. falciparum parasites plays a key role in mediating the pathology of malaria, transporting cyto-adherent ligands to the surface of infected erythrocytes and erythrocyte invasion ligands to specialized organelles within the parasite. However, many aspect of P. falciparum secretion are poorly understood, particularly the export of proteins to the erythrocyte surface and membrane-bound organelles within the erythrocyte cytosol, a transport step that is unique to P. falciparum biology. Furthermore, fundamental questions about the number and nature of secretory organelles in the P. falciparum pathway remain unanswered. The broad objective of this application is to comprehensively define the basic organization of the P. falciparum secretory pathway and to clarify the role of vesicle targeting in protein transport to membrane-bound organelles that are unique to P. falciparum. t-SNAREs, membrane bound proteins that control the specificity of vesicle fusion, will be used as organelle-specific markers to fill these crucial gaps in our knowledge base. We have identified several putative t-SNAREs in the P. falciparum genome and established that at least one of these is exported to unique organelles that appear in the cytosol of P. falciparum infected erythrocytes and mediate protein transport to the erythrocyte surface. The localization of and targeting signals in P. falciparum t-SNAREs will be investigated under the following specific aims: 1. Establish the sequence and location of the P. falciparum t-SNAREs. 2. Understand the molecular basis ofPfSynS targeting to the Maurer's clefts. An array of molecular, cellular and biochemical tools will be used to complete these aims, including immunofluorescence microscopy, sub-cellular fractionation and epitope tagging. This research is significant because it will be the first study of t-SNAREs and vesicle targeting in P. falciparum and may help clarify long- standing disputes about the basic structure of the P. falciparum secretory pathway. By focusing on elements of P. falciparum secretion that are unique to this organism, we aim to identify targets for the future development of novel prevention and control measures.

描述（由申请人提供）：每年疟原虫寄生虫造成超过100万人死亡，这是全球社区面临的最重要的公共卫生挑战之一。血液阶段恶性疟原虫的分泌途径在介导疟疾的病理学，将细胞粘附的配体转移到感染的红细胞表面和红细胞侵袭配体的表面中起着关键作用。然而，恶性疟原虫分泌的许多方面知之甚少，尤其是将蛋白质出口到红细胞胞质醇内的红细胞表面和膜结合的细胞器中，这是恶性疟原虫生物学特有的运输步骤。此外，关于恶性疟原虫途径中分泌细胞器的数量和性质的基本问题仍未得到解答。该应用的广泛目的是全面定义恶性疟原虫分泌途径的基本组织，并阐明囊泡靶向在蛋白质传输到恶性疟原虫所特有的蛋白质传输中的作用。 T-SNARES是控制囊泡融合特异性的膜结合蛋白，将用作细胞器特异性标记物，以填补我们的知识库中这些关键差距。我们已经确定了恶性疟原虫基因组中的几种假定的T-snares，并确定其中至少一个导出到出现在恶性疟原虫感染的红细胞细胞胞质中的独特细胞器中，并介导蛋白质的蛋白质转运到erythrocyte表面。在以下特定目的下，将研究恶性疟原虫T-snares中的定位和靶向信号的定位：1。建立恶性疟原虫T-snares的序列和位置。 2。了解靶向毛勒氏裂缝的pfsyns的分子基础。将使用一系列分子，细胞和生化工具来完成这些目标，包括免疫荧光显微镜，亚细胞分级和表位标记。这项研究很重要，因为它将是恶性疟原虫靶向T-snares和囊泡的首次研究，并可能有助于阐明有关恶性疟原虫分泌途径的基本结构的长期纠纷。通过专注于这种生物体独有的恶性疟原虫分泌的元素，我们旨在确定未来开发新型预防和控制措施的目标。