α-Synuclein has been implicated in the pathology of certain neurodegenerative diseases, including Parkinson disease (PD) and dementia with Lewy bodies (LBs). Overexpression of human α-synuclein in neuronal cells reduces cell viability, but the precise cellular and molecular mechanisms remain poorly understood. Gap junctional intercellular communication (GJIC) is thought to be essential for maintaining cellular homeostasis and growth control. In the present study, the effect of α-synuclein overexpression on GJIC in human dopaminergic neuroblastoma SH-SY5Y cells was investigated. Cells overexpressing wild-type α-synuclein were more vulnerable to hydrogen peroxide and 6-hydroxydopamine. GJIC was decreased in cells overexpressing α-synuclein. In addition, α-synuclein binds directly to connexin-32 (Cx32). As such, the post-translational modification of Cx32 was enhanced in cells overexpressing α-synuclein. These findings suggest that α-synuclein can modulate GJIC in a dopaminergic neuronal cell line through specific binding to Cx32.
Bibliographical noteFunding Information:
The authors are grateful to M.M. Mouradian and S.S. Scherer for providing cells and plasmids. This study was supported by a grant (M103KV010011-06K2201-01110 to K.C.C.) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of Republic of Korea, by a Basic Research Grant of Korea Science and Engineering Foundation (R01-2004-000-10673-0 to K.C.C.), and partly by grants (A050181 and A060440 to K.C.C.) from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea, and partly by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2004-005-E00017 to K.C.C).
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