Fibroblast growth factor-2 regulates the stability of nuclear bodies
Fibroblast growth factor-2 regulates the stability of nuclear bodies
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DOI：
10.1073/pnas.0900122106
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发表时间：
2009-08-04
影响因子：
11.1
通讯作者：
Claus, Peter
中科院分区：
文献类型：
--
作者：
Bruns, Alexander-Francisco;van Bergeijk, Jeroen;Claus, Peter
核体是不同的亚核结构。神经退行性疾病脊髓性肌萎缩症（SMA）患者的运动神经元存活（SMN）基因发生突变或缺失。基因产物 SMN 是一类称为核宝石的核体的标记蛋白。 SMN 也在卡哈尔体中被发现，它与许多细胞类型中的宝石共存。有趣的是，SMA 患者的宝石数量减少了。关于核体形成和稳定的调节知之甚少。我们之前已经证明，成纤维细胞生长因子-2 (FGF-2(23)) 的核亚型直接与 SMN 结合。在本研究中，我们分析了 FGF-2(23) 与 SMN 结合对核体形成的影响。在分子水平上，我们表明 FGF-2(23) 与 Gemin2（SMN 复合物的一个组成部分，是宝石稳定所必需的）竞争与 SMN 的结合。 siRNA 下调 Gemin2 导致 SMN 阳性核体不稳定。这一过程通过 FGF-2 在核体形成中的负调节功能在细胞和体内系统中得到反映：在 HEK293 细胞中，FGF-2(23) 减少了 SMN 阳性核体的数量。在 FGF-2 转基因小鼠的运动神经元中也可以观察到相同的效果。这项研究证明了生长因子在细胞核结构实体调节中的功能作用。
Nuclear bodies are distinct subnuclear structures. The survival of motoneuron (SMN) gene is mutated or deleted in patients with the neurodegenerative disease spinal muscular atrophy (SMA). The gene product SMN is a marker protein for one class of nuclear bodies denoted as nuclear gems. SMN has also been found in Cajal bodies, which co-localize with gems in many cell types. Interestingly, SMA patients display a reduced number of gems. Little is known about the regulation of nuclear body formation and stabilization. We have previously shown that a nuclear isoform of the fibroblast growth factor-2 (FGF-2(23)) binds directly to SMN. In this study, we analyzed the consequences of FGF-2(23) binding to SMN with regard to nuclear body formation. On a molecular level, we showed that FGF-2(23) competed with Gemin2 (a component of the SMN complex that is necessary for gem stabilization) for binding to SMN. Down-regulation of Gemin2 by siRNA caused destabilization of SMN-positive nuclear bodies. This process is reflected in both cellular and in vivo systems by a negative regulatory function of FGF-2 in nuclear body formation: in HEK293 cells, FGF-2(23) decreased the number of SMN-positive nuclear bodies. The same effect could be observed in motoneurons of FGF-2 transgenic mice. This study demonstrates the functional role of a growth factor in the regulation of structural entities of the nucleus.