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microRNAs （miRs）对基因表达的转录后控制允许在发育、分化和肿瘤细胞中对蛋白质表达进行时空微调。在发育中的神经元中经常观察到mRNA翻译的空间控制，并且需要将翻译沉默的mRNA转运到神经突中。据推测，这一过程是通过细胞质蛋白- rna复合物促进的，通常被归类为mRNPs。rna结合IGF2BP （IGF2 mRNA结合蛋白）蛋白家族的成员，也被称为zbp （Zipcode结合蛋白），是发育神经元中空间控制蛋白合成的重要调节因子。在后者，成纤维细胞和肿瘤来源细胞中，ZBP1控制ß-actin (ACTB) mRNA的翻译和在某些情况下的转运。src介导的ZBP1酪氨酸磷酸化激活了ACTB mRNA的翻译。在神经元生长锥中，ACTB蛋白合成的这种空间控制被认为是直接生长锥的突出和引导。根据所提出的项目，我们打算表征含有zbp1的mRNPs的组成和翻译后修饰，以时空方式破译它们在指导ACTB mRNA翻译中的作用。

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.