Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication
文献类型：期刊论文
| 作者 | Xie, YY; Zhou, CJ; Zhou, ZR; Hong, J; Che, MX; Fu, QS; Song, AX; Lin, DH; Hu, HY |
| 刊名 | FASEB JOURNAL
 |
| 出版日期 | 2010 |
| 卷号 | 24期号:1页码:196-205 |
| 关键词 | coiled coil solution structure Parkinson's disease Lewy body dimerization N-terminal stretch |
| 通讯作者 | Hu, HY (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,hyhu@sibs.ac.cn |
| 英文摘要 | alpha-Synuclein (alpha-Syn) is the major component of Lewy bodies (LBs) deposited in the brains of patients with Parkinson's disease. Synphilin-1 (Sph1) is a novel alpha-Syn-interacting protein also present in the LBs. However, the roles of alpha-Syn-Sph1 interaction in LB formation and in the related pathogenesis are still unclear. We have studied the interaction between alpha-Syn and Sph1 by biochemical and structural approaches and found that the central coiled-coil domain of Sph1 specifically interacts with the N-terminal stretch of alpha-Syn. When overexpressed in HEK 293T cells, Sph1 forms inclusions together with alpha-Syn, but the Sph1positive inclusions cannot recruit the N-terminally truncated alpha-Syn. The central portion of Sph1 can also recruit alpha-Syn and induce inclusion formation through its coiled-coil domain. These observations demonstrate that the alpha-Syn-Sph1 interaction significantly promotes the formation of cytoplasmic alpha-Syn inclusions, which may have implications for LB formation in neural cells. We have also elucidated solution structure of the coiled-coil domain of Sph1 and its interaction with the N-terminal peptide of alpha-Syn. The specific interaction between alpha-Syn and Sph1 provides mechanistic insights into the inclusion-body formation in cells and pathological implication in Parkinson's disease. Xie, Y.-Y., Zhou, C.-J., Zhou, Z.-R., Hong, J., Che, M.-X., Fu, Q.-S., Song, A.-X., Lin, D.-H., and Hu, H.-Y. Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication. FASEB J. 24, 196-205 (2010). www.fasebj.org |
| 学科主题 | Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biology ; Cell Biology |
| 关键词[WOS] | PARKINSONS-DISEASE ; LEWY BODIES ; NEUROBLASTOMA-CELLS ; AGGRESOME FORMATION ; CHEMICAL-SHIFT ; WILD-TYPE ; PROTEIN ; AGGREGATION ; NMR ; MUTATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000273233600021 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/931]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Xie, YY,Zhou, CJ,Zhou, ZR,et al. Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication[J]. FASEB JOURNAL,2010,24(1):196-205. |
| APA | Xie, YY.,Zhou, CJ.,Zhou, ZR.,Hong, J.,Che, MX.,...&Hu, HY.(2010).Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication.FASEB JOURNAL,24(1),196-205. |
| MLA | Xie, YY,et al."Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication".FASEB JOURNAL 24.1(2010):196-205. |
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