Molecular mechanisms of ARF family GTPases

ARF家族GTP酶的分子机制

• 批准号: 9893466
• 负责人: Richard A Kahn
• 金额: $ 9.54万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893466
• 关键词: Arl proteins; Biochemical; Biological; Cell physiology; Cells; Cellular biology; Centrosome; Cilia; Cytoskeleton; Cytosol; Energy Metabolism; Family; Functional disorder; Guanosine Triphosphate Phosphohydrolases; Heart Diseases; Human; Intervention; Malignant Neoplasms; Membrane Protein Traffic; Mitochondria; Molecular; Nerve Degeneration; Phylogenetic Analysis; Regulation; Retinal Degeneration; Signal Transduction; Site; System; ciliopathy; cilium biogenesis; deafness; human disease; insight; member; novel

Project Summary/Abstract Members of the ARF family of regulatory GTPases function as nodes in cell signaling to coordinate essential cell processes; including membrane traffic, energy metabolism, ciliogenesis, and the cytoskeleton. I have studied first ARF and later ARF-like (ARL) proteins for over 30 years, using a combination of biochemical, cell and molecular biological, and phylogenetic approaches and propose to continue these studies with a focus on their actions at specific sites; including mitochondria, cytosol, cilia, and centrosomes. We will both study mechanisms by which one GTPase acts in multiple sites in the same cells, to explore the potential for cross-talk or higher level ordering of cell signaling, but also explore novel, single actions for atypical GTPases as a means of determining shared or unique mechanisms within the family. A better understanding of these systems will reveal novel insights into fundamental aspects of cell biology as well as providing potential targets for intervention to alter the course of human diseases; including but not limited to cancer, heart disease, neurodegeneration, ciliopathies, retinal degeneration, and deafness.

项目摘要/摘要 调节GTPases的ARF家族的成员在细胞信号中起淋巴结功能 协调必需的细胞过程；包括膜交通，能源代谢， 纤毛生成和细胞骨架。我已经研究了第一个ARF，然后研究了类似ARF的（ARL）蛋白 30多年来，使用生化，细胞和分子生物学以及 系统发育方法并建议继续这些研究，重点是 特定站点；包括线粒体，细胞质，纤毛和中心体。我们都会研究 一个GTPase在同一细胞中多个位点作用的机制，以探索 细胞信号传导的串扰或更高水平排序的潜力，但也探索新颖的单个单一 非典型GTPases的动作，作为确定共享或独特机制的一种手段 一家人。对这些系统的更好理解将揭示对基本的新见解 细胞生物学的各个方面以及提供干预的潜在目标来改变过程 人类疾病；包括但不限于癌症，心脏病，神经变性， 纤毛病，视网膜变性和耳聋。