LYSOSOMAL PHYSIOLOGY & PROTEIN DEGRADATION IN CYSTINOSIS

不同营养条件下细胞蛋白质水解的调控机制 条件仍然知之甚少，虽然蛋白质之间的平衡， 合成和降解似乎是一个基本要求， 活细胞以在整个细胞周期中提供稳态。 许多 研究了各种蛋白质的溶酶体和非溶酶体蛋白水解， 蛋白质产生了相互矛盾的结果。 我们建议调查 细胞蛋白水解，利用独特的特性， 人类的突变，胱氨酸病，导致这些不能 一旦胱氨酸形成，细胞将其运输出溶酶体 其中来自含胱氨酸蛋白质的降解。 我们将准备 纯化的蛋白质在它们的细胞中用35 S-胱氨酸代谢标记， 二硫键部分，并研究产生的溶酶体35 S-胱氨酸 在将它们引入到 通过内吞作用、胞饮作用或显微注射作用使细胞内的蛋白质水平发生变化。 结果 应该加强我们对基因座和调控机制的理解， 细胞蛋白水解

The regulatory mechanisms for cellular proteolysis under varied nutritional conditions remain poorly understood, although a balance between protein synthesis and degradation would appear to be a fundamental requirement of living cells to provide homeostasis throughout the cell cycle. Numerous studies of the lysosomal and nonlysosomal proteolysis of a variety of proteins have produced conflicting results. We propose to investigate cellular proteolysis by taking advantage of the unique characteristic of the human mutation, cystinosis, which results in the inability of these cells to transport cystine out of the lysosome once it has been formed there from the degradation of cystine-containing proteins. We will prepare purified proteins metabolically labelled with 35S-cystine in their disulfide moieties and study the resultant lysosomal 35S-cystine accumulation in cystinotic fibroblasts produced after introducing them to the cell via endocytosis, pinocytosis or microinjection. The results should enhance our understanding of the loci and regulatory mechanisms of cellular proteolysis.