MOLECULAR IDENTITY OF MATURE LYSOSOMAL ACID SPHINGOMYELINASE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 酸性鞘磷脂酶(ASMase)催化鞘磷脂(SM)的水解形成具有生物活性的脂质神经酰胺(Cer)。值得注意的是，aSMase以两种形式存在--锌不依赖的溶酶体aSMase(L-sMase)和锌依赖的分泌型aSMase(S-sMase)，它们来自单一蛋白前体的替代运输。尽管对aSMase的成熟和转运进行了广泛的研究，但成熟的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的分子同一性，特别是C-末端的蛋白降解过程。羧基末端加工代表了aSMase翻译后调控的一种新机制，这对L-SMase的活性和功能的调控具有重要意义，并可能为揭示尼曼-皮克病的分子基础提供新的视角。

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.