MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 7379911
• 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/7379911
• 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 Program; Generations; Genetic; Genetic Screening; Genetic Techniques; Golgi Apparatus; Growth; Hydrolysis; Image; Laboratories; Link; Mammals; Membrane; Membrane Protein Traffic; Methods; Microfilaments; Microscopy; Microtubules; Minority; Mitochondrial Inheritance; Molecular Motors; Morphology; Motor; Movement; Mutation; Myosin Type V; 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

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.

蛋白质和细胞器的正确分布是真核细胞的基本特性。这种“极性” 使它们能够经历分裂、极化生长和分化等过程。一种方法你可以 通过引导膜运输来建立极性。该调节是从酵母到 哺乳动物，因此可以在酵母中揭示其发生的基本原理，然后在其中进行研究 动物模型的更多细节。我建议研究 4-磷酸磷脂酰肌醇 (PI4P) 在 分泌，特别是评估其在 Myo2p 活性中的作用。 Myo2p 是负责运动的运动蛋白 细胞周期中几种细胞成分的运动和分离。其货物之一是 分泌囊泡，起源于高尔基体。大量证据表明PI4P是主要PI 高尔基体中的物种，而且我们有初步的遗传和成像数据表明 PI4P 可能发挥着重要作用 在 Myo2p 依赖性分泌囊泡运输中的作用。我计划通过各种遗传来进一步研究这一点 技术，即过表达抑制分析、突变体的产生和表征等。 另外，使用酵母二杂交和常规生化测定的改良版本，我将尝试 识别难以捉摸的分泌囊泡 Myo2 受体。我的结果以及实验室的其他人 在其他地方，将有助于我们了解 Myo2p 的调节方式，这对于细胞的生存至关重要。