Dendritic localization of the translational repressor Pumilio 2 and its contribution to dendritic stress granules
Dendritic localization of the translational repressor Pumilio 2 and its contribution to dendritic stress granules
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DOI：
10.1523/jneurosci.0649-06.2006
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发表时间：
2006-06-14
影响因子：
5.3
通讯作者：
Macchi, Paolo
中科院分区：
文献类型：
--
作者：
Vessey, John P.;Vaccani, Angelo;Macchi, Paolo
Pumilio(Pum)蛋白在酵母、果蝇、非洲爪哇和哺乳动物等多种生物中起翻译抑制作用。两个Pumilio基因，Pum1和Pum2，已经在哺乳动物中被发现，但它们在神经元中的功能还没有被确定。在本研究中，我们发现Pum2mRNA在神经元发育过程中表达，该蛋白存在于完全极化的神经元的胞体和树突室的离散颗粒中。这一发现表明Pum2是一种新的树枝状定域核糖核微粒(RNPs)候选者。在代谢应激期间，Pum2存在于应激颗粒(SGS)中，随后在躯体树突体内检测到SGS。它在任何情况下都被排除在处理机构之外。当Pum2在神经元和成纤维细胞中过表达时，它可以诱导SGS的形成，其中还包括T细胞胞内抗原1(TIA-1)相关蛋白、真核启动因子4E、聚(A)结合蛋白、TIA-1以及其他RNA结合蛋白，包括Staufen1和Barentsz。这种SGS的诱导依赖于Pum2的RNA结合区和N端的谷氨酰胺富集区。这个富含谷氨酰胺的区域的行为方式类似于TIA-1和普恩蛋白，这两个分子在蛋白质聚集中具有已知的作用。在代谢应激过程中，Pum2通过RNA干扰(RNAi)在神经元中下调，干扰SGS的形成。与Pum2 mRNA的RNAi抗性部分共转染可恢复SG的形成。这些结果表明Pum2在哺乳动物神经元的树突状RNPs和SG的形成中起作用。
Pumilio (Pum) protein acts as a translational inhibitor in several organisms including yeast, Drosophila, Xenopus, and mammals. Two Pumilio genes, Pum1 and Pum2, have been identified in mammals, but their function in neurons has not been identified. In this study, we found that Pum2 mRNA is expressed during neuronal development and that the protein is found in discrete particles in both the cell body and the dendritic compartment of fully polarized neurons. This finding indicates that Pum2 is a novel candidate of dendritically localized ribonucleoparticles (RNPs). During metabolic stress, Pum2 is present in stress granules (SGs), which are subsequently detected in the somatodendritic domain. It remains excluded from processing bodies under all conditions. When overexpressed in neurons and fibroblasts, Pum2 induces the formation of SGs that also contain T-cell intracellular antigen 1 (TIA-1)-related protein, eukaryotic initiation factor 4E, poly(A)-binding protein, TIA-1, and other RNA-binding proteins including Staufen1 and Barentsz. This induction of SGs is dependent on the RNA-binding domain and a glutamine-rich region in the N terminus of Pum2. This glutamine-rich region behaves in a similar manner as TIA-1 and prion protein, two molecules with known roles in protein aggregation. Pum2 downregulation in neurons via RNA interference (RNAi) interferes with the formation of SGs during metabolic stress. Cotransfection with an RNAi-resistant portion of the Pum2 mRNA restores SG formation. These results suggest a role for Pum2 in dendritic RNPs and SG formation in mammalian neurons.