Neural Control of Proteolysis in Specific Muscle Cells

9630841雅各布森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--秀丽线虫身上进行，这种线虫的肌肉和神经细胞相对较少，可以进行遗传实验。在这些实验中，一种报告基因被引入到生物体中，因为其蛋白质产物的降解很容易被跟踪。这位研究人员此前发现，这种蛋白质在喂养良好的动物中是稳定的，但在饥饿时会分解。这种不稳定性被神经传递给肌肉的信号所抵消。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(在之前的一项研究中)表明，该信号涉及神经释放乙酰胆碱，肌肉表面接收该信号，以及随后从肌肉内储存的钙离子释放。钙离子通过刺激蛋白激酶C(PKC)来起作用，从而减缓蛋白质分解的速度。在这项提案中，将寻求PKC作用的更多证据，将确定PKC的作用目标，并将进行实验以确定PKC如何减缓蛋白质分解的速度。这种动物中接收不同化学信号的一组不同的肌肉细胞将被检查，以查看是否有相同或不同的信号系统在运行。蛋白质降解的调节是一个重要的问题，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. ***