Cambray Serafí, Pedraza Neus, Rafel Marta, Garí Eloi, Aldea Martí, Gallego Carme
Departament de Ciències Mèdiques Bàsiques, IRBLLEIDA, Universitat de Lleida, Lleida, Catalonia, Spain.
Mol Cell Biol. 2009 Feb;29(3):726-35. doi: 10.1128/MCB.01180-08. Epub 2008 Nov 17.
The regulation of mRNA transport is a fundamental process for cytoplasmic sorting of transcripts and spatially controlled translational derepression once properly localized. There is growing evidence that translation is locally modulated as a result of specific synaptic inputs. However, the underlying molecular mechanisms that regulate this translational process are just emerging. We show that KIS, a serine/threonine kinase functionally related to microtubule dynamics and axon development, interacts with three proteins found in RNA granules: KIF3A, NonO, and eEF1A. KIS localizes to RNA granules and colocalizes with the KIF3A kinesin and the beta-actin mRNA in cultured cortical neurons. In addition, KIS is found associated with KIF3A and 10 RNP-transported mRNAs in brain extracts. The results of knockdown experiments indicate that KIS is required for normal neurite outgrowth. More important, the kinase activity of KIS stimulates 3' untranslated region-dependent local translation in neuritic projections. We propose that KIS is a component of the molecular device that modulates translation in RNA-transporting granules as a result of local signals.
mRNA转运的调控是转录本在细胞质中进行分选以及一旦正确定位后在空间上进行可控的翻译去抑制的一个基本过程。越来越多的证据表明，翻译会因特定的突触输入而受到局部调节。然而，调节这一翻译过程的潜在分子机制才刚刚开始显现。我们发现，KIS是一种与微管动力学和轴突发育功能相关的丝氨酸/苏氨酸激酶，它与RNA颗粒中发现的三种蛋白质相互作用：KIF3A、NonO和eEF1A。KIS定位于RNA颗粒，并与培养的皮层神经元中的KIF3A驱动蛋白和β-肌动蛋白mRNA共定位。此外，在脑提取物中发现KIS与KIF3A和10种RNP转运的mRNA相关联。敲低实验结果表明，KIS是正常神经突生长所必需的。更重要的是，KIS的激酶活性刺激了神经突投射中3'非翻译区依赖性的局部翻译。我们提出，KIS是一种分子装置的组成部分，该装置可根据局部信号调节RNA转运颗粒中的翻译。
