内源性G蛋白偶联受体激酶对HEK293细胞中α-突触核蛋白Ser129磷酸化的作用。
Contribution of endogenous G-protein-coupled receptor kinases to Ser129 phosphorylation of alpha-synuclein in HEK293 cells.
作者信息
Sakamoto Masahiro, Arawaka Shigeki, Hara Susumu, Sato Hiroyasu, Cui Can, Machiya Youhei, Koyama Shingo, Wada Manabu, Kawanami Toru, Kurita Keiji, Kato Takeo
机构信息
Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
出版信息
Biochem Biophys Res Commun. 2009 Jul 3;384(3):378-82. doi: 10.1016/j.bbrc.2009.04.130. Epub 2009 May 3.
The majority of alpha-synuclein (alphaS) deposited in Lewy bodies, the pathological hallmark of Parkinson's disease (PD), is phosphorylated at serine 129 (Ser129). Ser129 phosphorylation of alphaS has been demonstrated to enhance the alphaS toxicity to dopaminergic neurons in a Drosophila model of PD. Phosphorylation of alphaS at Ser129 seems to play a crucial role in the pathogenesis of PD. Here, we assessed the contribution of ubiquitously expressing members of the G-protein-coupled receptor kinase family (GRK2, GRK3, GRK5, and GRK6) to Ser129 phosphorylation of alphaS in HEK293 cells. To selectively reduce the endogenous expression of each member of the GRK family in cells, we used small interfering RNAs. Knockdown of GRK3 or GRK6 significantly decreased Ser129 phosphorylation of alphaS; however, knockdown of GRK2 or GRK5 did not decrease alphaS phosphorylation. The results indicate that endogenous GRK3 and GRK6, but not GRK2 or GRK5, contribute to Ser129 phosphorylation of alphaS in HEK293 cells.
沉积在路易小体（帕金森病（PD）的病理标志）中的大多数α-突触核蛋白（αS）在丝氨酸129（Ser129）处发生磷酸化。在PD果蝇模型中，αS的Ser129磷酸化已被证明会增强αS对多巴胺能神经元的毒性。αS在Ser129处的磷酸化似乎在PD的发病机制中起关键作用。在此，我们评估了G蛋白偶联受体激酶家族（GRK2、GRK3、GRK5和GRK6）的泛素表达成员对HEK293细胞中αS的Ser129磷酸化的作用。为了选择性降低细胞中GRK家族每个成员的内源性表达，我们使用了小干扰RNA。敲低GRK3或GRK6可显著降低αS的Ser129磷酸化；然而，敲低GRK2或GRK5并未降低αS磷酸化。结果表明，内源性GRK3和GRK6而非GRK2或GRK5，对HEK293细胞中αS的Ser129磷酸化有作用。
Zotero 插件