Role of Sec7 Domain Guanine Nucleotide Exchange Factors in Membrane Traffic

Sec7 域鸟嘌呤核苷酸交换因子在膜运输中的作用

• 批准号: 1050852
• 负责人: Elizabeth Sztul
• 金额: $ 97.64万
• 依托单位: University of Alabama at Birmingham
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1050852&HistoricalAwards=false
• 关键词: Role; Sec7; Domain; Guanine; Nucleotide

Intellectual MeritMembrane traffic mediates secretion and the delivery of proteins and lipids to intracellular organelles and the plasma membrane. The mechanisms regulating this process are largely conserved throughout all eukaryotes and what is learned in one species can reveal events occurring in other species (including humans). In unicellular organisms, membrane traffic sustains cell growth and interactions with the environment. In multicellular organisms, membrane traffic is required for deposition of the extracellular matrix and cell adhesion, the release and uptake of growth factors and nutrients, and the insertion of environment sensing receptor and signal transducers, i.e., all the processes that integrate the developmental and physiological responses of tissues and organs. This project will focus on key regulators of membrane traffic, the ADP-ribosylation factor (ARF) GTPases. Specifically, the mechanisms and molecules that facilitate ARF activation will be identified and characterized. This project studies the molecular mechanisms that regulate membrane trafficking to understand a process essential for cellular and organismal life.Broader ImpactsThe broader impacts of this project are: (1) Training and mentoring of postdoctoral fellows, graduate students and undergraduates in cutting-edge molecular, imaging, biochemical and genetic technologies to probe key questions in cellular physiology. (2) Promoting scientific equity by actively recruiting and mentoring under-represented groups to enter scientific careers. (3) Promoting interdisciplinary synergy by interfacing with structural and biophysical scientists to provide additional cross-field fertilization of technologies and ideas. (4) Promoting global scientific infrastructure by developing and disseminating plasmids, antibodies, recombinant proteins and experimental approaches to labs worldwide. This project has additional societal benefits because it will provide the next generation of academic researchers and teachers, improve the competitiveness of US scientific enterprise and prepare highly trained individuals for non-academic jobs in science and education.

智能优点膜运输介导蛋白质和脂质的分泌和递送到细胞内细胞器和质膜。调节这一过程的机制在所有真核生物中都很大程度上是保守的，在一个物种中学到的东西可以揭示其他物种（包括人类）中发生的事件。 在单细胞生物中，膜运输维持细胞生长和与环境的相互作用。在多细胞生物体中，细胞外基质的沉积和细胞粘附、生长因子和营养素的释放和摄取以及环境传感受体和信号转导物的插入需要膜运输，即，所有整合组织和器官的发育和生理反应的过程。该项目将集中在膜运输的关键调节剂，ADP-核糖基化因子（ARF）GTP酶。具体而言，机制和分子，促进ARF激活将被确定和表征。 本项目主要研究调节细胞膜运输的分子机制，以了解细胞和生物体生命所必需的过程。更广泛的影响本项目的更广泛的影响是：（1）培训和指导博士后研究员，研究生和本科生在尖端分子，成像，生物化学和遗传技术，以探索细胞生理学的关键问题。(2)通过积极招募和指导代表性不足的群体进入科学职业，促进科学公平。(3)通过与结构和生物物理科学家的交流促进跨学科的协同作用，以提供更多的技术和想法的跨领域施肥。(4)通过开发和向世界各地的实验室传播质粒、抗体、重组蛋白和实验方法，促进全球科学基础设施。该项目具有额外的社会效益，因为它将提供下一代学术研究人员和教师，提高美国科学企业的竞争力，并为科学和教育领域的非学术工作准备训练有素的个人。