ATP13A2 deficiency induces a decrease in cathepsin D activity, fingerprint‐like inclusion body formation, and selective degeneration of dopaminergic neurons. Issue 9 (13th March 2013)

• Record Type: Journal Article
• Authors: Matsui, Hideaki; Sato, Fumiaki; Sato, Shigeto; Koike, Masato; Taruno, Yosuke; Saiki, Shinji; Funayama, Manabu; Ito, Hidefumi; Taniguchi, Yoshihito; Uemura, Norihito; Toyoda, Atsushi; Sakaki, Yoshiyuki; Takeda, Shunichi; Uchiyama, Yasuo; Hattori, Nobutaka; Takahashi, Ryosuke
• Is Part Of: FEBS letters. Volume 587:Issue 9(2013)
• Page Start: 1316
• Page End: 1325
• Publication Date: 2013-03-13
• Subjects: Parkinson's disease -- Medaka fish -- ATP13A2 -- Lysosome; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.02.046
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : ATP13A2 is a lysosomal protein but some disease-associated variants remain in the endoplasmic reticulum. Loss of ATP13A2 function in cells results in cell death, cathepsin D reduction and fingerprint-like structures. Atp13a2 mutant medaka discloses dopaminergic cell death, cathepsin D reduction and fingerprint-like structures.