The role of the protein phosphatase PPM1G in the regulation of nuclear functions of the SMN complex

蛋白磷酸酶PPM1G在SMN复合体核功能调节中的作用

• 批准号: 72209666
• 负责人: Professor Dr. Oliver Gruß
• 金额: --
• 依托单位: Abteilung Zellteilung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/72209666?language=en
• 关键词: role; protein; phosphatase; PPM1G; regulation

The biogenesis of Uridine-rich small nuclear ribonucleoprotein particles (UsnRNPs) is a complicated process, which requires assembly and maturation steps in the nucleus and in the cytoplasm. Assembly in the cytoplasm is an active process mediated by a macromolecular entity called the SMN complex. The SMN complex is imported together with the snRNPs into the nucleus, where SMN complex proteins accumulate in Cajal bodies (CBs), while snRNPs end up in specialised splicing compartments ("speckles"). Very little is known about the regulation of nuclear functions of the SMN complex. We have identified a nuclear phosphatase, PPM1G, the knock-down of which results in complete abolishment of the accumulation of the SMN complex in CBs. PPM1G directly interacts with the SMN complex and is responsible compartment specific dephosphorylation of SMN complex proteins. Identification of PPM1G enables us to specifically search for kinase activities, which phosphorylate components of the SMN complex and which are required for SMN accumulation in CBs. We are also aiming to identify amino acid residues in SMN complex proteins, which are responsible for this regulation. In the second part of our project, we are going to test whether PPM1G knock-down changes the dynamics of SMN within the nucleus and, possibly, regulates its capability to return to the cytoplasm. Furthermore, we will test SMN and PPMIGs role to help maturation of UsnRNPs. Finally, we are going to investigate the function of PPM1G and other phosphatases in the regulation of the nuclear splicing machinery.

富含尿苷的小核核糖核蛋白颗粒（UsnRNP）的生物发生是一个复杂的过程，它需要在细胞核和细胞质中的组装和成熟步骤。细胞质中的组装是由称为SMN复合物的大分子实体介导的主动过程。SMN复合物与snRNP一起输入细胞核，SMN复合物蛋白在卡哈尔体（CB）中积累，而snRNP最终进入专门的剪接区室（“斑点”）。关于SMN复合体的核功能的调节知之甚少。我们已经确定了一个核磷酸酶，PPM1G，敲低的结果在完全废除的积累的SMN复合物在CB。PPM1G直接与SMN复合物相互作用，并负责SMN复合物蛋白的隔室特异性去磷酸化。PPM1G的鉴定使我们能够特异性地搜索激酶活性，其磷酸化SMN复合物的组分并且其是CB中SMN积累所需的。我们还旨在确定SMN复合蛋白中负责这种调节的氨基酸残基。在我们项目的第二部分中，我们将测试PPM1G敲低是否会改变细胞核内SMN的动态，并可能调节其返回细胞质的能力。此外，我们将测试SMN和PPMIG在帮助UsnRNP成熟方面的作用。最后，我们将研究PPM1G和其他磷酸酶在调节核剪接机制中的功能。