Department of Molecular Biology, Sejong University, 98 Gunja-dong, Kwangjin-gu, Seoul 143-747, Republic of Korea.
Biochem Biophys Res Commun. 2012 Aug 3;424(3):497-502. doi: 10.1016/j.bbrc.2012.06.143. Epub 2012 Jul 4.
α-Synuclein is the major component of Lewy bodies and Lewy neurites, the pathological hallmarks of surviving neuronal cells in Parkinson's disease patients. However, the physiological role played by α-synuclein remains unclear. In this study, spectrin beta non-erythrocyte 1 (SPTBN1) interacted with α-synuclein in phage display assays using a normalized human brain cDNA library. A direct interaction between α-synuclein and SPTBN1 was confirmed by GST pull-down and co-immunoprecipitation assays. SPTBN1 and α-synuclein proteins colocalized in N2a neuronal cells. Transfection of SPTBN1 caused human SH-SY5Y dopaminergic neuron cells to inappropriately induce neurites, which extended from cell bodies. Cotransfection with α-synuclein reversed SPTBN1-induced excessive neurite branching in SH-SY5Y cells, and only a single neurite extended from each neuron. These results suggest that α-synuclein modulates neurite outgrowth by interacting with cytoskeletal proteins such as SPTBN1.
α-突触核蛋白是路易体和路易神经突的主要成分，是帕金森病患者存活神经元细胞的病理标志。然而，α-突触核蛋白的生理作用尚不清楚。在这项研究中，使用标准化的人类大脑 cDNA 文库，在噬菌体展示实验中， spectrin beta non-erythrocyte 1（SPTBN1）与 α-突触核蛋白相互作用。通过 GST 下拉和共免疫沉淀实验证实了 α-突触核蛋白和 SPTBN1 之间的直接相互作用。SPTBN1 和 α-突触核蛋白蛋白在 N2a 神经元细胞中发生共定位。转染 SPTBN1 导致人 SH-SY5Y 多巴胺能神经元细胞不恰当地诱导神经突从细胞体延伸。与 α-突触核蛋白共转染可逆转 SH-SY5Y 细胞中 SPTBN1 诱导的过度神经突分支，并且每个神经元仅从单个神经元延伸。这些结果表明，α-突触核蛋白通过与细胞骨架蛋白如 SPTBN1 相互作用来调节神经突生长。
