Table of Contents
ISRN Neurology
Volume 2011 (2011), Article ID 732879, 6 pages
Research Article

Serine 129 Phosphorylation of α-Synuclein Cross-Links with Tissue Transglutaminase to Form Lewy Body-Like Inclusion Bodies

1Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
2Dpartment of Neurology, The First People's Hospital of Foshan, Foshan 528000, China
3Department of Pathophysiology, School of Medicine, JiNan University, Guangzhou 510632, China
4Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA

Received 28 January 2011; Accepted 16 March 2011

Academic Editor: T. B. Sherer

Copyright © 2011 Wei Bi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Intraneuronal depositions of α-synuclein have been implicated in the pathogenesis of Parkinsons's disease (PD). Previous reports have identified the crosslinking between α-synuclein and tTG (tissue transglutaminase) in both PD patients and the cellular model. However, no researches have been conducted to further investigate their interaction in physiological conditions. To address this question, we generated the SH-SY5Y cell line which stably expressed the wild-type or mutant (Ser129Ala) α-synuclein. After the treatment with okadaic acid, α-synuclein started forming aggregates upon the activation of tTG. Coimmunoprecipitation assays revealed a decreased interaction of the mutant α-synuclein S129A with tTG compared with the wild-type α-synuclein. Cells expressing the wild-type α-synuclein showed increased eosinophilic cytoplasmic inclusion bodies that resembled Lewy bodies compared with the mutant. Double immunofluorescence staining confirmed the colocalization of the phosphorylated α-synuclein and the tTG in the cells. The S129A mutant demonstrated a lesser degree of colocalization than the wild type.