MOLECULAR STUDIES ON THE MANNOSE 6-PHOSPHATE RECEPTOR

溶酶体是正常细胞降解的主要场所 选民。超过30种可遗传的“储藏疾病”是由 溶酶体水解酶活性的特殊缺陷。有缺陷的溶酶体 机能也是衰老的特点，营养多样 精神错乱。获得性疾病中的溶酶体损伤导致 激活的水解酶的胞外释放，这通常会导致坏死 和细胞死亡。 甘露糖6-磷酸受体负责定位许多 溶酶体中的水解酶。它会立即与水解酶结合 合成并便于将其包装成溶酶体。感受器 也在细胞表面起作用，以促进酸性水解酶的去除 从胞外部位。 长期目标是确定甘露糖的分子基础。 6-磷酸受体功能。重组DNA技术将用于 在介绍受体的结构变化时，将使用生物方法 以考察它们对受体功能的特定方面的影响。这个 这一提议的直接目标是克隆一种编码 甘露糖6-磷酸受体并确定该受体的结构， 为实现这一目标提供基础。这些研究将有助于 根据我们对溶酶体生物发生的理解，细胞内膜 贩卖和蛋白质分类。

Lysosomes are the primary site for degradation of normal cellular constituents. Over 30 inheritable "storage diseases" are caused by specific defects in lysosomal hydrolase activities. Defective lysosomal function is also characteristic of aging and various nutritional disorders. Lysosomal injury during acquired diseases results in extracellular release of activated hydrolase which often produces necrosis and cell death. The mannose 6-phosphate receptor is responsible for localization of many hydrolases in lysosomes. It binds the hydrolases immediately after their synthesis and facilitates their packaging into lysosomes. The receptor also functions on the cell surface to facilitate removal of acid hydrolases from extracellular sites. The long range goal is to determine the molecular basis of mannose 6-phosphate receptor function. Recombinant DNA techniques will be used to introduce structural changes in the receptor, biologic methods will be used to examine their effects on specific aspects of receptor function. The immediate objectives of this proposal, namely to clone a cDNA encoding the mannose 6-phosphate receptor and determine the structure of the receptor, provide the basis for achieving this goal. These studies will contribute to our understanding of lysosome biogenesis, intracellular membrane trafficking and protein sorting.