Phagocytic Removal of Apoptotic Cells

凋亡细胞的吞噬去除

• 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
• 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

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(申请人提供)：在动物发育和成年过程中，细胞发生凋亡，这是一个对动物发育和动态平衡至关重要的细胞死亡过程，通过吞噬(吞噬)迅速被其他细胞内化，并在吞噬细胞内降解。去除凋亡细胞为清除体内不需要的和危险的细胞提供了一种安全的方法。此外，它还可以防止组织损伤、炎症反应和自身免疫反应，这些反应可能是由死亡细胞的含量引起的。去除凋亡细胞的研究也激励了新的癌症治疗策略的发展。我的长期目标是以线虫秀丽线虫为模式生物，了解控制凋亡细胞识别、吞噬和降解的分子机制。我们相信，从线虫身上学到的东西将被转化为人类。这些项目研究的是驱动凋亡细胞降解的机制，这些细胞被内化到宿主细胞中，被限制在一种被称为“吞噬小体”的空泡结构中。吞噬小体通过一系列的膜转运事件经历一个“成熟”的过程，最终结果是腔内货物的降解。我们的研究将揭示磷脂酰肌醇3-磷酸(PI3P)在吞噬体上的产生(目标1)和周转(目标2)的时间调节机制，以及PI3P如何触发成熟过程(目标3)。我们对PI3P信号转导机制的研究不仅有助于揭示PI3P介导的其他膜转运事件的分子机制，包括内吞转运和自噬，也将有助于揭示PI3P介导的其他膜转运的分子机制。