MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 7176834
• 负责人: Felipe H Santiago-Tirado
• 金额: $ 3.81万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7176834
• 关键词: Actins; Affect; Alleles; Animal Model; Binding; Biochemical; Biological Assay; Cell Cycle; Cell Survival; Cell division; Cell membrane; Data; Defect; Differentiation and Growth; Elements; Endocytosis; Epithelium; Equilibrium; Eukaryotic Cell; Family; Fellowship; Fellowship Program; Generations; Genetic; Genetic Screening; Genetic Techniques; Golgi Apparatus; Growth; Hydrolysis; Image; Individual; Laboratories; Link; Mammals; Membrane; Membrane Protein Traffic; Methods; Microfilaments; Microscopy; Microtubules; Minority; Mitochondrial Inheritance; Molecular Motors; Morphology; Motor; Movement; Mutation; Myosin Type V; Names; Nuclear; Nutrient; Organelles; Phosphatidylinositols; Phosphoric Monoester Hydrolases; Phosphotransferases; Play; Process; Property; Protein Overexpression; Proteins; Regulation; Reporting; Role; Saccharomycetales; Secretory Vesicles; Specificity; Tail; Transport Vesicles; Vacuole; Yeasts; cell motility; genetic analysis; in vivo; mutant; peroxisome; phosphatidylinositol 4-phosphate; pre-doctoral; protein distribution; protein function; receptor; segregation; vesicle/vacuole; yeast two hybrid system

DESCRIPTION (provided by applicant): Proper distribution of proteins and organelles is an essential property of eukaryotic cells. This "polarity" allows them to undergo processes like division, polarized growth, and differentiation. One way you can establish polarity is by directing membrane traffick. This regulation is a conserved process from yeast to mammals, so the basic principles of how that is occurring can be uncovered in yeast and then studied in more detail in animal models. I propose to study the role of phosphatidylinositol-4-phosphate (PI4P) in secretion, specifically, to evaluate its role in Myo2p activity. Myo2p is the motor protein responsible for the movement and segregation of several cellular components during the cell cycle. One of its cargoes is the secretory vesicles, that originate from the Golgi. Abundant evidence indicate that PI4P is the major PI species in the Golgi, plus we have preliminary genetic and imaging data suggesting that PI4P may play a role in Myo2p-dependent secretory vesicle transport. I plan to investigate this further by various genetic techniques, namely overexpression suppression analysis, generation and characterization of mutants, etc. Also, using modified versions of the yeast two-hybrid and conventional biochemical assays, I will try to identify the elusive secretory vesicle Myo2-receptor. My results, together with others in the lab and elsewhere, will help our understanding of how Myo2p is regulated, which is essential for the cell's survival.

描述（由申请人提供）：蛋白质和细胞器的正确分布是真核细胞的重要特性。这种“极性”使他们能够经历分裂，极化生长和分化等过程。您可以建立极性的一种方法是指导膜贩运。该调节是从酵母到哺乳动物的保守过程，因此可以在酵母中发现发生这种情况的基本原理，然后在动物模型中进行更详细的研究。我建议研究磷脂酰肌醇-4-磷酸（PI4P）在分泌中的作用，特别是评估其在MyO2p活性中的作用。 MyO2p是负责在细胞周期中几个细胞成分运动和分离的运动蛋白。它的货物之一是分泌囊泡，源自高尔基体。大量证据表明，PI4P是高尔基体中的主要PI物种，而且我们有初步的遗传和成像数据，表明PI4P可能在MyO2P依赖性分泌囊泡运输中起作用。我计划通过各种遗传技术，即过表达抑制分析，突变体的产生和表征等进一步研究此事。而且，使用酵母两杂交和常规生化测定的修改版本，我将尝试识别难以捉摸的分泌囊泡肌肌2-受体。我的结果与实验室和其他地方的其他人一起，将有助于我们对Myo2p的调节方式的理解，这对于细胞的生存至关重要。