Prion Protein and Its Ligand Stress Inducible Protein 1 Regulate Astrocyte Development
Prion Protein and Its Ligand Stress Inducible Protein 1 Regulate Astrocyte Development
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DOI：
10.1002/glia.20861
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发表时间：
2009-10-01
期刊：
影响因子：
6.2
通讯作者：
Martins, Vilma R.
中科院分区：
文献类型：
--
作者：
Arantes, Camila;Nomiz, Regina;Martins, Vilma R.
朊病毒蛋白 (PrPC) 与应激诱导蛋白 1 (STI1) 的相互作用介导神经元存活和分化。然而，星形胶质细胞中 PrPC 的功能尚未被探讨。在这项研究中，我们发现 STI1 以蛋白激酶 A 依赖性方式阻止野生型星形胶质细胞的细胞死亡，而 PrPC 无效的星形胶质细胞不受 STI1 处理的影响。在胚胎第 17 天，与野生型相比，培养的星形胶质细胞和来自 PrPC 缺失小鼠的脑提取物显示胶质原纤维酸性蛋白 (GFAP) 表达减少，波形蛋白和巢蛋白表达增加，表明 PrPC 缺失动物中星形胶质细胞成熟速度较慢。此外，用STI1处理的PrPC无效星形胶质细胞并没有像野生型星形胶质细胞那样从扁平形态分化为带有突起的形态。值得注意的是，STI1 以蛋白激酶 C 依赖性方式抑制野生型和 PrPC-null 星形胶质细胞的增殖。总而言之，我们的数据表明 PrPC 和 STI1 对于星形胶质细胞的发育至关重要，并通过不同的信号通路发挥作用。(C) 2009 Wiley-Liss, Inc.
Prion protein (PrPC) interaction with stress inducible protein 1 (STI1) mediates neuronal survival and differentiation. However, the function of PrPC in astrocytes has not been approached. In this study, we show that STI1 prevents cell death in wild-type astrocytes in a protein kinase A-dependent manner, whereas PrPC-null astrocytes were not affected by STI1 treatment. At embryonic day 17, cultured astrocytes and brain extracts derived from PrPC-null mice showed a reduced expression of glial fibrillary acidic protein (GFAP) and increased vimentin and nestin expression when compared with wild-type, suggesting a slower rate of astrocyte maturation in PrPC-null animals. Furthermore, PrPC-null astrocytes treated with STI1 did not differentiate from a flat to a process-bearing morphology, as did wild-type astrocytes. Remarkably, STI1 inhibited proliferation of both wild-type and PrPC-null astrocytes in a protein kinase C-dependent manner. Taken together, our data show that PrPC and STI1 are essential to astrocyte development and act through distinct signaling pathways.(C) 2009 Wiley-Liss, Inc.