Signaling pathways that regulate cytoskeletal dynamics in Caenorhabditis elegans

人体的骨骼、软骨、肌肉和肌腱为个体提供灵活性和运动。在细胞水平上，细胞骨架通过协调各种细胞形状变化和运动，包括细胞分裂、细胞迁移、细胞生长和细胞内运输，发挥同等的功能。但是是什么调节了细胞骨架动力学？这种变化是如何开始的？本研究计划旨在回答这些问题。具体来说，我们专注于阐明允许外部信号中包含的信息被细胞吸收并传递给细胞骨架以引起细胞形状变化的遗传途径和细胞机制。我们过去的研究确定了UNC-53和导航（NAVs），这是一种在蠕虫和人类中都发现的蛋白质家族，它们调节细胞的迁移，发育过程中神经元和细胞过程的生长，以及细胞中分子在其生命周期中的持续运输。随后对新型分子相互作用的表征和细胞迁移和生长的实时成像研究表明，nav在细胞骨架组装点发挥其活性。但是是什么指示UNC-53/ nav这样做的呢？当前提案中概述的研究主要有两个重点：首先，识别细胞内调节UNC-53/NAV活性的外部信号和细胞表面受体；其次，了解UNC-53/ nav在细胞内运输中的功能。Wnt家族的信号分子是极好的候选UNC-53激活剂。Wnt基因的突变会产生类似的缺陷

The bones, cartilage, muscles and tendons of the human body provide flexibility and movement to the individual. At the cellular level, the cytoskeleton performs an equivalent function, by orchestrating a variety of cellular shape changes and movements, including cell division, cell migration, cell outgrowth, and intracellular transport. But what regulates cytoskeleton dynamics and how is this change initiated? This research proposal is aimed at answering these questions. Specifically, we are focused at elucidating the genetic pathways and cellular mechanisms that allows the information contained in an external signal to be assimilated by the cell and relayed to the cytoskeleton to invoke cell shape changes. Our past research identified UNC-53 and the Navigators (NAVs), a family of proteins found in both worms and humans that regulate the migration of cells, the outgrowth of neuronal and cellular processes during development, and the ongoing transport of molecules in the cell during its lifetime. The subsequent characterization of novel molecular interactions and live imaging studies of cell migrations and outgrowth have suggested that NAVs exert their activity at the point of cytoskeleton assembly. But what instructs UNC-53/NAVs to do this?  There are two main thrusts of the research outlined in the current proposal: firstly, to identify the external signals and cell surface receptors that regulate UNC-53/NAV activity inside the cell; and, secondly, to understand the function of UNC-53/NAVs in intracellular transport. The Wnt family of signaling molecules are excellent candidate UNC-53 activators. Mutations in Wnt genes generate similar defects observed in