MOLECULAR IDENTITY OF MATURE LYSOSOMAL ACID SPHINGOMYELINASE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 酸性鞘磷脂酶（aSMase）催化鞘磷脂（SM）水解形成生物活性脂质神经酰胺（Cer）。值得注意的是，aSM酶以两种形式存在-锌（Zn）非依赖性溶酶体aSM酶（L-SM酶）和Zn依赖性分泌型aSM酶（S-SM酶），其由单一蛋白质前体的交替运输产生。尽管对aSMase的成熟和运输进行了广泛的研究，但成熟L-SMase的确切身份仍然不清楚。我们感兴趣的是确定成熟的L-SMase的分子身份，特别是C-末端蛋白水解加工。羧基末端加工可能是aSMase翻译后调控的一种新机制，对L-SMase活性和功能的调控具有重要意义，并可能为尼曼-匹克病的分子基础提供新的见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Acid sphingomyelinase (aSMase) catalyzes the hydrolysis of sphingomyelin (SM) to form the bioactive lipid ceramide (Cer). Notably, aSMase exists in two forms - a zinc (Zn)-independent lysosomal aSMase (L-SMase) and a Zn-dependent secreted aSMase (S-SMase) that arise from alternative trafficking of a single protein precursor. Despite extensive investigation into the maturation and trafficking of aSMase, the exact identity of mature L-SMase has remained unclear. We are interested in determining the molecular identity of mature L-SMase, specifically C-terminal proteolytic processing. Carboxy-terminal processing would represent a novel mechanism of post-translational regulation of aSMase, which has implications for the regulation of L-SMase activity and function, and may provide new insight into the molecular basis of Niemann-Pick disease.