LYSOSOMAL RETOOLING DURING DIFFERENTIATION

分化过程中的溶酶体重组

• 批准号: 3445951
• 负责人: Stephen J. FREE
• 金额: $ 5.16万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3445951
• 关键词: Dictyostelium; O glycosidase; acid phosphatase; alpha glucosidase; antibody formation; beta galactosidase; cell differentiation; enzyme structure; enzyme therapy; gel electrophoresis; immunoprecipitation; inborn metabolism disorder; mannosidase; metabolism disorder chemotherapy; monoclonal antibody; oligosaccharides; proteolysis; radiotracer

We propose studying the changing of protein modification that occurs on a number of lysosomal enzymes during differentiation. The dictyostelial lysosome has been considered an excellent model for the lysosomes of higher organisms. The alteration of protein modification structure affects the configuration of these lysosomal enzymes and could affect enzymatic properties, in vivo stability, and secretion. This "retooling" of preexisting molecules represents a means to rapidly alter the organelle during the process of differentiation. We will characterize the alterations occuring to the enzymes and determine how the alterations affect the fate of the various enzymes. Human congenital diseases such as l-cell disease, Fabry's disease, Niemann-Pick disease, and Gaucher's disease have been shown to be due to deficiencies in lysosomal enzymes. We expect this grant to give information relating to what characteristics of post-translational modification are needed to protect a lysosomal enzyme from being degraded within the lysosome. Such information would be valuable in enzyme replacement therapy to correct a lysosomal enzyme deficiency. The incoming replacement enzyme needs to be stable within the lysosome for an extended period of time.

我们建议研究发生在 分化过程中溶酶体酶的数量。 网状体 溶酶体被认为是高等溶酶体的优秀模型 有机体。 蛋白质修饰结构的改变影响 这些溶酶体酶的构型可能会影响酶促反应 性质、体内稳定性和分泌。 此次“重组” 预先存在的分子代表了快速改变细胞器的一种手段 在分化的过程中。 我们将表征 酶发生的改变并确定改变是如何发生的 影响各种酶的命运。 人类先天性疾病如 l 细胞病、法布里病、尼曼-皮克病和戈谢病 已证明疾病是由于溶酶体酶的缺乏引起的。 我们 希望这笔赠款能够提供有关以下特征的信息： 需要翻译后修饰来保护溶酶体酶 以免在溶酶体内被降解。 此类信息将是 在纠正溶酶体酶的酶替代疗法中有价值 不足。 引入的替代酶需要在范围内稳定 溶酶体作用时间较长。

项目成果

A developmentally controlled change in the post-translational modifications on the lysosomal alpha-mannosidase of the cellular slime mould Dictyostelium discoideum.

细胞粘菌盘基网柄菌溶酶体α-甘露糖苷酶翻译后修饰的发育控制变化。

• DOI: 10.1042/bj2430739
• 发表时间: 1987
• 期刊: The Biochemical journal
• 作者: Moore,BR;Vladutiu,G;Free,SJ
• 通讯作者: Free,SJ

Developing Dictyostelium discoideum cells contain two distinct acid hydrolase-containing vesicles.

发育中的盘基网柄菌细胞含有两个不同的含有酸性水解酶的囊泡。

• DOI: 10.1016/0014-4827(89)90295-4
• 发表时间: 1989
• 期刊: Experimental cell research
• 影响因子: 3.7
• 作者: Lenhard,JM;Kasperek,E;Moore,BR;Free,SJ
• 通讯作者: Free,SJ

Changes in the post-translational modification of lysosomal enzymes during development of Dictyostelium.

盘基网柄菌发育过程中溶酶体酶翻译后修饰的变化。

• DOI: 10.1111/j.1432-0436.1985.tb00285.x
• 发表时间: 1985
• 期刊: Differentiation; research in biological diversity
• 作者: Moore,BR;Gossels,SD;Free,SJ
• 通讯作者: Free,SJ