Role of autophagy and retromer genes in GLP-1/Notch signaling

自噬和逆转录酶基因在 GLP-1/Notch 信号传导中的作用

• 批准号: 8367474
• 负责人: Alicia Melendez
• 金额: $ 31万
• 依托单位: QUEENS COLLEGE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8367474
• 关键词: Address; Affect; Aging; Amino Acids; Animals; Antibodies; Autophagocytosis; Autophagosome; Biological Models; Caenorhabditis elegans; Cell Cycle Regulation; Cell Differentiation process; Cell Fate Control; Cell Proliferation; Cell Proliferation Regulation; Cells; Competence; Data; Degradation Pathway; Development; Endocytosis; Ensure; Evolution; Fc Receptor; Frequencies; Gene Silencing; Genes; Genetic; Germ Cells; Goals; Grant; Growth; Homeostasis; Image; Insulin; Insulin-Like Growth Factor I; Label; Laboratories; Life; Ligands; Link; Lipids; Longevity; Mammals; Meiosis; Metabolism; Mitosis; Modeling; Nature; Notch Signaling Pathway; Nutrient; Organelles; Organism; Orthologous Gene; Pathway interactions; Phenotype; Positioning Attribute; Process; Proliferating; Property; Proteins; RNA Interference; Recycling; Regulation; Reporter; Reproduction; Role; Signal Pathway; Signal Transduction; Starvation; Stress; Testing; Tissues; Yeasts; biological systems; cell fate specification; developmental genetics; gain of function; gene function; glucagon-like peptide 1; in vivo; mutant; notch protein; novel; nutrition; positional cloning; receptor; reproductive function; stem cell fate specification; stem cell population

DESCRIPTION (provided by applicant): The control of cell proliferation of stem cell population of cells in the germline is a fundamental property of biological systems that requires an exquisite level of regulation to ensure normal reproductive function. Sexual reproduction of multicellular organisms depends on a number of germ cells that decide whether to differentiate or to continue to divide (meiosis vs. mitosis). The regulation of cell proliferation may require a number of external signals, such as nutrition or stress conditions, which may impact on the regulation of the competence to proliferate, a poorly understood aspect of cell fate specification, as well as the regulation of mitosis and the control of the cell-cycle. The C. elegans germline is a valuable model to study the genetic, developmental, and environmental control of germ cell proliferation. Because of the fundamental nature of growth control, its regulation is likely to be conserved through evolution, enabling the use of simple, genetically tractable organisms as model systems. A conserved GLP-1/Notch signaling pathway controls the cell fate decision to retain proliferative competence or to differentiate by entering meiosis. In this study, we will elucidate the role of autophagy and other endocytic pathways on GLP-1/Notch signaling. Specifically, our proposal aims to: (1) define the role of autophagy and retromer activity during C. elegans development, specifically in the regulation of the glp-1/Notch signaling in the development of the germline, and to (2) elucidate the role of endocytic genes in the formation of an autophagosome, in dauer development and during germline development. These studies are significant because they will advance our understanding of the mechanisms by which autophagy functions in the development of a multicellular organism, and in the control of cell proliferation. They will be informative regarding both the tissues that require autophagy in development and the proteins involved in the signaling pathway. Our laboratory is uniquely positioned to pursue this project with our expertise in C. elegans genetics and the study of autophagy. PUBLIC HEALTH RELEVANCE: This study aims to explore the role of autophagy - a cellular pathway by which cytoplasmic components are recycled - in germline development by examining links between autophagy, retromer function and the Notch/GLP-1 signaling pathway.

描述（由申请人提供）：控制细胞增殖的干细胞群体的细胞在生殖系是一个基本的特性，需要一个精湛的生物系统