Nerve Growth Cone Locomotion

生长轴突最重要的部分可能是其顶端的结构，即生长锥。神经生长锥对于轴突定向生长至关重要。它们是复杂的感觉-运动机器，通过细胞表面受体或离子通道通透性的变化对环境线索作出反应。它们在局部使用信号转导途径处理这些信息，这些信号转导途径调节负责在环境中前进的运动机制。相对而言，我们对整合这些信息并调节其对运动的影响的具体机制知之甚少。尽管信号转导途径已被涉及，但很难将这些途径与持续存在的特定运动效应机制联系起来。一种效应机制是肌凝蛋白产生的力。肌凝蛋白活性具有多种作用，包括控制生长锥形状的变化和产生推动向前发展的牵引力。它是一个

Probably the most important part of the growing axon is the structure at its tip, the growth cone. Nerve growth cones are essential for directed axonal outgrowth. They are complex sensory-motor machines that respond to environmental cues through cell surface receptors or changes in ion channel permeability. They locally process this information using signal transduction pathways that regulate the motility mechanism responsible for driving forward advancement through the environment. Relatively little is known about the specific mechanisms that integrate the information and regulate its affect on motility. Although signal transduction pathways have been implicated, it has been difficult to link these pathways to specific effecter mechanisms of motility that persist over time. One effecter mechanism is the generation of force by myosin. Myosin activity has multiple roles that include the control of growth cone shape changes and the generation of traction force that drives forward advancement. It is an important effecter of growth cone motility that may be essential for changes in direction of advancement. My overall goal is to identify the various myosins responsible for modulating growth cone motility, understand how pathways that are stimulated by specific environmental cues control myosin activity and how the force that is developed is coupled to the extracellular environment to provide traction force. I propose that myosin II is the most important of the myosins identified in growth cones for regulating motility and producing traction force. I will test this proposal by eliminating the activity of myosin II and then measuring key aspects of motility including traction force. I also plan to identify the major pathways involved in growth cone myosin II regulation. Combined these results will provide the framework for understanding the molecular basis of growth cone motility and how environmental cues stimulate specific pathways to regulate this motility. This is essential for understanding the formation of neuronal circuitry during development and the mechanisms required for successful nerve regeneration.