Saposin C Protects Glucocerebrosidase against α-Synuclein Inhibition

被引：38
|
作者：
Yap, Thai Leong [1 ]
Gruschus, James M. [1 ]
Velayati, Arash [2 ]
Sidransky, Ellen [2 ]
Lee, Jennifer C. [1 ]
机构：
[1] NHLBI, Lab Mol Biophys, Biochem & Biophys Ctr, Bethesda, MD 20892 USA
[2] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA
来源：
BIOCHEMISTRY | 2013年 / 52卷 / 41期
基金：
美国国家卫生研究院;
关键词：
SPHINGOLIPID ACTIVATOR PROTEINS; NEURONOPATHIC GAUCHER-DISEASE; LYSOSOMAL STORAGE; BETA-GLUCOSIDASE; DEFICIENCY; MUTATIONS; RECONSTITUTION; ACCUMULATION; DEGRADATION; MODEL;
D O I：
10.1021/bi401191v
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Mutations in GBA1, the gene for glucocerebrosidase (GCase), are genetic risk factors for Parkinson disease (PD). alpha-Synuclein (alpha-Syn), a protein implicated in PD, interacts with GCase and efficiently inhibits enzyme activity. GCase deficiency causes the lysosomal storage disorder Gaucher disease (GD). We show that saposin C (Sap C), a protein vital for GCase activity in vivo, protects GCase against alpha-syn inhibition. Using nuclear magnetic resonance spectroscopy, site-specific fluorescence, and Forster energy transfer probes, Sap C was observed to displace alpha-syn from GCase in solution and on lipid vesicles. Our results suggest that Sap C might play a crucial role in GD-related PD.
引用
收藏
页码：7161 / 7163
页数：3
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