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Original Article

Exp Neurobiol 2014; 23(4): 365-371

Published online December 31, 2014

© The Korean Society for Brain and Neural Sciences

ATP13A2/PARK9 Deficiency Neither Cause Lysosomal Impairment Nor Alter α-Synuclein Metabolism in SH-SY5Y Cells

Eun-Jin Bae1,2, Cheolsoon Lee2,3, He-Jin Lee2,3, Seokjoong Kim4 and Seung-Jae Lee1,2,5,*

1Department of Biomedical Science and Technology, 2Institute of Biomedical Science and Technology,
3Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701,
4ToolGen, Inc., Biotechnology Incubating Center, Seoul National University, Seoul 305-390,
5College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-447-5685, FAX: 82-2-447-5683

Received: October 24, 2014; Revised: November 12, 2014; Accepted: November 13, 2014


Parkinson's disease is a multifactorial disorder with several genes linked to the familial types of the disease. ATP13A2 is one of those genes and encode for a transmembrane protein localized in lysosomes and late endosomes. Previous studies suggested the roles of this protein in lysosomal functions and cellular ion homeostasis. Here, we set out to investigate the role of ATP13A2 in lysosomal function and in metabolism of α-synuclein, another PD-linked protein whose accumulation is implicated in the pathogenesis. We generated non-sense mutations in both copies of ATP13A2 gene in SH-SY5Y human neuroblastoma cells. We examined lysosomal function of ATP13A2-/- cells by measuring the accumulation of lysosomal substrate proteins, such as p62 and polyubiquitinated proteins, induction of acidic compartments, and degradation of ectopically introduced dextran. None of these measures were altered by ATP13A2 deficiency. The steady-state levels of α-synuclein in cells or secretion of this protein were unaltered either in ATP13A2-/- compared to the normal cells. Therefore, the proposed roles of ATP13A2 in lysosomal functions may not be generalized and may depend on the cellular context. The ATP13A2-/- cells generated in the current study may provide a useful control for studies on the roles of PD genes in lysosomal functions.

Keywords: ATP13A2, PARK9, Lysosome, Parkinson’s disease, alpha-synuclein, SH-SY5Y cell