期刊
FEBS LETTERS
卷 587, 期 9, 页码 1316-1325出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2013.02.046
关键词
Parkinson's disease; Medaka fish; ATP13A2; Lysosome
资金
- JST-CREST
- Ministry of Education, Science, Sports and Culture of Japan
- Grants-in-Aid for Scientific Research [23129506, 23590244, 25461291, 23790238] Funding Source: KAKEN
Kufor-Rakeb syndrome (KRS) was originally described as an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia. ATP13A2 was identified as the causative gene in KRS. ATP13A2 encodes the ATP13A2 protein, which is a lysosomal type5 P-type ATPase, and ATP13A2 mutations are linked to autosomal recessive familial parkinsonism. Here, we report that normal ATP13A2 localizes in the lysosome, whereas disease-associated variants remain in the endoplasmic reticulum. Cathepsin D activity was decreased in ATP13A2-knockdown cells that displayed lysosome-like bodies characterized by fingerprint-like structures. Furthermore, an atp13a2 mutation in medaka fish resulted in dopaminergic neuronal death, decreased cathepsin D activity, and fingerprint-like structures in the brain. Based on these results, lysosome abnormality is very likely to be the primary cause of KRS/PARK9. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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