Wnt/Wg Extracellular Ligand Distribution and Regulation

Wnt/Wg 细胞外配体分布和调节

• 批准号: 9054616
• 负责人: Andrea W Page-McCaw
• 金额: $ 32.19万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9054616
• 关键词: Behavior Control; Biological Models; Cell Culture Techniques; Cell Differentiation process; Cell Proliferation; Cell Survival; Cell membrane; Cell physiology; Cells; Cleaved cell; Complex; Data; Development; Diffuse; Diffusion; Distal; Drosophila genus; Endocytosis; Environment; Event; Family; Frequencies; Genes; Genetic; Glypican; Homeostasis; Ligands; Maintenance; Matrix Metalloproteinases; Mediating; Modeling; Molecular; Organ; Ovary; Paper; Pathway interactions; Peptide Hydrolases; Population; Process; Production; Protein Inhibition; Proteins; Proteolysis; Regulation; Signal Transduction; Signaling Molecule; Signaling Protein; Site; Source; Stem cells; Tissues; Wnt proteins; Work; animal tissue; cell behavior; cell type; egg; extracellular; germline stem cells; mutant; notch protein; novel; protein transport; public health relevance; receptor; response; stem cell niche; trafficking; tumor

 DESCRIPTION (provided by applicant): Extracellular signaling ligands are highly potent and can induce responses in many cell types. Many ligands, such as the conserved Wnt family of signaling ligands, are active at both high and low concentrations. Because they can function so broadly, it is essential that tissues and organs control the extracellular levels and diffusion of these signaling proteins. In this proposal, we investigate how a Wnt protein emanating from a single source functions in in the Drosophila ovary to signal differentially to proximal cells and distal cells. Our analysis shows that this Wnt pool regulates both the germline and follicle stem cells, which must ultimately coordinate to build an egg. Both types of Wnt signaling are altered by a new molecular module, composed of the glypican Dally-like protein (Dlp) and a matrix metalloproteinase (Mmp2). In the first Aim, we analyze how the Dlp/Mmp2 module has different functions in regulating proximal and distal Wnt signaling. In the second Aim we investigate how Dlp trafficking is altered by Mmp2 at a cellular level. In the third Aim we investigate how a small group of Wnt-secreting cells coordinate their production by "taking turns" maintaining constant extracellular levels of Wnt protein. This work is significant in understanding how tissues harness potent extracellular signals to perform multiple tasks.