Human α-synuclein modulates vesicle trafficking through its interaction with prenylated Rab acceptor protein 1
Human α-synuclein modulates vesicle trafficking through its interaction with prenylated Rab acceptor protein 1
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DOI：
10.1016/j.bbrc.2011.07.028
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发表时间：
2011-09-09
影响因子：
3.1
通讯作者：
Im, Hana
中科院分区：
文献类型：
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作者：
Lee, Hak Joo;Kang, Shin Jung;Im, Hana
α-突触核蛋白与帕金森病的发病机制有关。尽管它高度保守，但其生理功能尚未详细阐明。为了确定 α-突触核蛋白的功能，在噬菌体展示测定中筛选了相互作用的蛋白质。异戊二烯化 Rab 受体蛋白 1 (PRA1) 被确定为相互作用伙伴。通过免疫共沉淀和 GST Pull-down 测定证实了 α-突触核蛋白和 PRA1 之间的选择性相互作用。 PRA1 和 α-突触核蛋白共定位于 N2a 神经元细胞中。 α-突触核蛋白和 PRA1 的共转染导致囊泡在神经元细胞的胞浆外周积聚，这表明由于 α-突触核蛋白和 PRA1 之间的相互作用，α-突触核蛋白的过度表达阻碍了囊泡的正常运输和再循环。 (C) 2011 Elsevier Inc. 保留所有权利。
alpha-Synuclein has been implicated in the pathogenesis of Parkinson's disease. Although it is highly conserved, its physiological function has not yet been elucidated in detail. In an effort to define the function of alpha-synuclein, interacting proteins were screened in phage display assays. Prenylated Rab acceptor protein 1 (PRA1) was identified as an interacting partner. A selective interaction between alpha-synuclein and PRA1 was confirmed by coimmunoprecipitation and GST pull-down assays. PRA1 and alpha-synuclein were colocalized in N2a neuronal cells. Cotransfection of alpha-synuclein and PRA1 caused vesicles to accumulate in the periphery of the cytosol in neuronal cells, suggesting that overexpression of alpha-synuclein hinders proper vesicle trafficking and recycling as a result of the interaction between alpha-synuclein and PRA1. (C) 2011 Elsevier Inc. All rights reserved.