Phagocytic Removal of Apoptotic Cells

凋亡细胞的吞噬去除

基本信息

批准号：
8515448
负责人：
Zheng Zhou
金额：
$ 32.85万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-05-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8515448
关键词：
1-Phosphatidylinositol 3-Kinase Adult Animal Model Animals Apoptosis Apoptotic Autophagocytosis Biological Assay Caenorhabditis elegans Cell Death Process Cells Chronic Development Digestion Dissociation Embryo Enhancers Event Excision Genes Genetic Genetic Screening Homeostasis Human Image Immune System Diseases Immune response Individual Inflammatory Inflammatory Response Injury Invaded Learning Left Life Light Lipids Lysosomes Mediating Membrane Protein Traffic Modeling Molecular Monitor Nematoda Organelles Pathway interactions Pattern Phagocytes Phagocytosis Phagosomes Phosphoric Monoester Hydrolases Play Process Production Protein Family Proteins Protocols documentation Recruitment Activity Regulation Role Second Messenger Systems Series Signal Pathway Signal Transduction Structure Surface Therapeutic Tissues Translating Work accomplished suicide cancer cell cancer therapy fighting member mutant neuronal cell body novel null mutation pathogen phosphatidylinositol 3-phosphate prevent protein protein interaction rab GTP-Binding Proteins receptor second messenger tool trafficking treatment strategy

项目摘要

DESCRIPTION (provided by applicant): During animal development and adulthood, cells undergoing apoptosis, a cell death process essential for animal development and homeostasis, are rapidly internalized by other cells via phagocytosis (engulfment) and degraded inside engulfing cells. The removal of apoptotic cells provides a safe means for eliminating unwanted and dangerous cells from the body. Furthermore, it prevents tissue injury, inflammatory responses, and auto-immune responses that could be induced by the content of dead cells. The study of apoptotic-cell removal has also inspired the development of novel cancer treatment strategies. My long-term objective is to understand the molecular mechanism that controls the recognition, engulfment, and degradation of apoptotic cells, using the nematode Caenorhabditis elegans as a model organism. We believe that what is learnt from C. elegans will be translated to humans. These project studies mechanisms that drive the degradation of apoptotic cells, which are internalized into host cells, confined in a vacuolar structure called "phagosome". Phagosomes undergo a "maturation" process through a series of membrane trafficking events and the end result is the degradation of cargos in the lumen. Our studies will reveal the temporal regulation mechanisms of the production (Aim 1) and turnover (Aim 2) of phosphatidylinositol 3-phosphate (PI3P), a lipid second messenger that plays an essential role in initiating phagosome maturation, on phagosomes, and how PI3P triggers the maturation process (Aims 3). Our study of the PI3P signaling mechanisms will shed light not only on the degradation of apoptotic cells, but also broadly, on the molecular mechanisms behind other PI3P-mediated membrane trafficking events, including endocytic trafficking and autophagy.

描述（由申请人提供）：在动物发育和成年期间，细胞凋亡的细胞是动物发育和稳态必不可少的细胞死亡过程，其他细胞通过吞噬作用（吞噬）迅速内化，并在吞噬细胞内降解。凋亡细胞的去除提供了一种安全的手段，可以消除体内不需要的和危险的细胞。此外，它可以防止通过死细胞含量引起的组织损伤，炎症反应和自身免疫反应。凋亡细胞去除的研究还激发了新型癌症治疗策略的发展。我的长期目标是了解使用线虫秀丽隐杆线虫作为模型有机体，了解控制凋亡细胞的识别，吞噬和降解的分子机制。我们相信，从秀丽隐杆线虫学到的东西将被转化为人类。这些驱动凋亡细胞降解的项目研究机制将内部化为宿主细胞，限制在称为“吞噬体”的液泡结构中。通过一系列膜运输事件，吞噬体经历了“成熟”过程，最终结果是腔内钙的降解。我们的研究将揭示生产的时间调节机制（AIM 1）和磷脂酰肌醇3-磷酸（PI3P）（PI3P），这是一种脂质的第二信使，在启动吞噬成熟，对吞噬体和PI3P触发如何触发吞噬成熟方面起着至关重要的作用。我们对PI3P信号传导机制的研究不仅会阐明凋亡细胞的降解，而且还广泛地介绍了其他PI3P介导的膜运输事件的分子机制，包括内吞运输和自噬事件。