Neural Control of Proteolysis in Specific Muscle Cells

小行星9630841 这项研究的目的是研究从神经接收的信号如何控制肌肉细胞中蛋白质的分解。 这些研究将在线虫中进行，秀丽隐杆线虫具有相对较少的肌肉和神经细胞，并且可以进行遗传实验。 对于这些实验，报告基因已被引入生物体中，因为其蛋白质产物的降解可以容易地跟踪。 该研究人员先前发现，这种蛋白质在喂养良好的动物中是稳定的，但在饥饿时被分解。这种不稳定性被从神经到肌肉的信号抵消。 这些实验旨在了解蛋白质分解的分子基础，控制它的神经信号，以及神经信号减少蛋白质分解的机制。早期的研究（在先前的资助中）表明，信号传导涉及神经释放乙酰胆碱，肌肉表面接收这种信号，以及随后从肌肉内释放钙离子。 钙离子通过刺激蛋白激酶C（PKC）来发挥作用，从而减缓蛋白质分解的速率。 在这个提议中，将寻找PKC作用的额外证据，确定PKC作用的靶点，并进行实验以确定PKC如何减慢蛋白质分解的速率。 在这种动物中，一组不同的肌肉细胞，接收不同的化学信号，将被检查，看看是否相同或不同的信号系统正在运作。 蛋白质降解的调节是一个重要问题，这些实验将有助于回答这个问题。 ***

9630841 Jacobson The objective of this research is to investigate how signals received from nerves control the breakdown of protein in muscle cells. These studies will be carried out in the nematode, Caenorhabditis elegans, which has relatively few muscle and nerve cells, and in which genetic experiments can be done. For these experiments a reporter transgene has been introduced into the organism, since the degradation of its protein product can be easily followed. This investigator previously found that this protein is stable in well-fed animals, but is broken down upon starvation. This instability is counteracted by signals from nerves to the muscles. These experiments are aimed at understanding the molecular basis of the protein breakdown, the nerve signals that control it, and the mechanism by which nerve signals decrease protein breakdown. Earlier studies (in a previous grant) showed that the signaling involves release of acetylcholine by the nerves, reception of this signal at the surface of the muscles, and the consequent release of calcium ions from storage inside the muscles. The calcium ions act by stimulating the enzyme protein kinase C (PKC) which slows the rate of protein breakdown. In this proposal additional evidence for the role of PKC will be sought, the targets of PKC action will be determined, and experiments will done to determine how PKC slows the rate of protein breakdown. A distinct group of muscle cells in this animal, that receives different chemical signals, will be examined to see whether the same or different signaling systems are operating. The regulation of protein degradation is an important question, which these experiments will help to answer. ***