title: Serine 129 Phosphorylation of α-Synuclein Cross-Links with Tissue Transglutaminase to Form Lewy Body-Like Inclusion Bodies.
abstract: 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.
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhang
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Sun
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhu
authors.forename: Chuanming
authors.initials: C
authors.lastname: Wang
authors.forename: Yanran
authors.initials: Y
authors.lastname: Liang
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Shi
authors.forename: Enxiang
authors.initials: E
authors.lastname: Tao