Molecular mechanisms of ARF family GTPases

项目总结/摘要 调节性GTP酶的ARF家族成员在细胞信号传导中起节点的作用， 协调基本细胞过程;包括膜运输，能量代谢， 纤毛发生和细胞骨架。我研究了第一个ARF和后来的ARF样（ARL）蛋白， 30多年来，使用生物化学，细胞和分子生物学的组合， 系统发育的方法，并建议继续这些研究，重点是他们的行动， 特定位点;包括线粒体、胞质溶胶、纤毛和中心体。我们都要学习 一种GTdR在同一细胞的多个位点发挥作用的机制，以探索 潜在的串扰或更高水平的细胞信号的排序，而且还探索新的，单一的 作为确定非典型全球贸易协定内部共享或独特机制的手段 家里对这些系统的更好理解将揭示对基本原理的新见解。 细胞生物学方面，以及提供干预的潜在目标，以改变 人类疾病;包括但不限于癌症，心脏病，神经变性， 睫状体病、视网膜变性和耳聋。

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.