Department of Life Sciences, Korea University, Seoul, 02841, Korea.
Department of Biotechnology, Hoseo University, Asan, 31499, Korea.
Sci Rep. 2017 Sep 22;7(1):12178. doi: 10.1038/s41598-017-12379-3.
Calcium and integrin binding protein 1 (CIB1) is a calcium-binding protein that was initially identified as a binding partner of platelet integrin α. Although CIB1 has been shown to interact with multiple proteins, its biological function in the brain remains unclear. Here, we show that CIB1 negatively regulates degeneration of dopaminergic neurons in a mouse model of Parkinson's disease using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Genetic deficiency of the CIB1 gene enhances MPTP-induced neurotoxicity in dopaminergic neurons in CIB1 mice. Furthermore, RNAi-mediated depletion of CIB1 in primary dopaminergic neurons potentiated 1-methyl-4-phenyl pyrinidium (MPP)-induced neuronal death. CIB1 physically associated with apoptosis signal-regulating kinase 1 (ASK1) and thereby inhibited the MPP-induced stimulation of the ASK1-mediated signaling cascade. These findings suggest that CIB1 plays a protective role in MPTP/MPP-induced neurotoxicity by blocking ASK1-mediated signaling.
钙整合素结合蛋白 1(CIB1)是一种钙结合蛋白,最初被鉴定为血小板整合素 α 的结合伴侣。尽管 CIB1 已被证明与多种蛋白质相互作用,但它在大脑中的生物学功能仍不清楚。在这里,我们使用 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)显示 CIB1 在帕金森病小鼠模型中负调控多巴胺能神经元的变性。CIB1 基因的遗传缺失增强了 CIB1 小鼠中多巴胺能神经元中 MPTP 诱导的神经毒性。此外,在原代多巴胺能神经元中 RNAi 介导的 CIB1 耗竭增强了 1-甲基-4-苯基吡啶(MPP)诱导的神经元死亡。CIB1 与凋亡信号调节激酶 1(ASK1)物理结合,从而抑制了 MPP 诱导的 ASK1 介导的信号级联的刺激。这些发现表明 CIB1 通过阻断 ASK1 介导的信号转导在 MPTP/MPP 诱导的神经毒性中发挥保护作用。