Asymmetric protein sorting via localizd translation - The role of ZBP protein in directing mRNA localization and translation

通过RNA结合蛋白（RBP）和microRNA（miR）对基因表达的转录后控制允许在发育、分化以及肿瘤细胞中对蛋白质表达进行时空微调。mRNA翻译的空间控制经常在发育中的神经元中观察到，并且需要将异常沉默的mRNA转运到神经突中。据推测，这一过程是通过细胞质蛋白质-RNA复合物，通常归类为mRNP促进。RNA结合IGF 2BP（IGF 2 mRNA结合蛋白）蛋白家族的成员，也称为ZBP（Zipcode结合蛋白），是发育神经元中空间控制蛋白质合成的重要调节因子。在后者中，成纤维细胞以及肿瘤衍生的细胞，ZBP 1控制翻译，并且在某些情况下控制肌动蛋白（ACTB）mRNA的转运。在Src介导的ZBP 1酪氨酸磷酸化后，ACTB mRNA翻译被激活。在神经元生长锥中，ACTB蛋白合成的空间控制被推测为指导生长锥突出和引导。随着项目的提出，我们打算表征ZBP 1的mRNP的组成和翻译后修饰，以破译其在时空方式指导ACTB mRNA翻译的作用。

Posttranscriptional control of gene expression by RNA-binding proteins (RBPs) and microRNAs (miRs) allows the spatiotemporal fine tuning of protein expression during development, differentiation but also in neoplastic cells. Spatial control of mRNA translation is frequently observed in developing neurons and requires the transport of translationally silenced mRNAs into neurites. It is assumed that this process is facilitated via cytoplasmic protein-RNA complexes, typically classified as mRNPs. Members of the RNA-binding IGF2BP (IGF2 mRNA binding protein) protein family, also termed ZBPs (Zipcode binding proteins), are essential regulators of spatially controlled protein synthesis in developing neurons. In the latter, fibroblasts but also tumor-derived cells, ZBP1 controls translation and in some cases transport of the ß-actin (ACTB) mRNA. Upon Src-mediated tyrosine phosphorylation of ZBP1, ACTB mRNA translation is activated. In neuronal growth cones this spatial control of ACTB protein synthesis is presumed to direct growth cone protrusion and guidance. With the projects proposed, we intend to characterize the composition and posttranslational modifications of ZBP1-containing mRNPs to decipher their role in directing ACTB mRNA translation in a spatiotemporal manner.