Molecular mechanisms of ARF family GTPases

ARF家族GTP酶的分子机制

• 批准号: 10001990
• 负责人: Richard A Kahn
• 金额: $ 49.01万
• 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/10001990
• 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.

项目概要/摘要 调节 GTP 酶 ARF 家族的成员在细胞信号传导中充当节点 协调重要的细胞过程；包括膜运输、能量代谢、 纤毛发生和细胞骨架。我首先研究了 ARF，后来研究了 ARF 样 (ARL) 蛋白 30多年来，结合生物化学、细胞和分子生物学， 系统发育方法并建议继续这些研究，重点关注它们在 特定地点；包括线粒体、细胞质、纤毛和中心体。我们俩都会学习 一种 GTPase 在同一细胞的多个位点发挥作用的机制，以探索 细胞信号传导的串扰或更高级别排序的潜力，但也探索新颖的、单一的 非典型 GTPases 的行动作为确定内部共享或独特机制的手段 家人。更好地理解这些系统将揭示对基本原理的新见解 细胞生物学的各个方面以及提供潜在的干预目标以改变细胞生物学的进程 人类疾病；包括但不限于癌症、心脏病、神经退行性疾病、 纤毛病、视网膜变性和耳聋。