Behar L, Marx R, Sadot E, Barg J, Ginzburg I
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Int J Dev Neurosci. 1995 Apr;13(2):113-27. doi: 10.1016/0736-5748(95)00001-w.
Tau microtubule-associated protein is a neuron specific protein found primarily in axons and is developmentally regulated. The function of tau is in stabilization of microtubules, which is important in establishing and maintaining neuronal morphology. Axonal localization of tau involves a multistep process which is studied in differentiating primary neuronal culture. The initial step involves sorting and subcellular localization of its encoding mRNA into the proximal portion of the axon. Using the transfection assay into neuronal cells, we have demonstrated that sequences located in the 3'-untranslated region include a cis-acting signal which is involved in tau mRNA targeting. In addition, using ultraviolet cross-linking assay, two RNA-binding proteins of 43 and 38 kDa were identified, that exhibit specific binding to a minimal sequence of 91 nucleotides located within the same functional region, which is involved in targeting. The 43 and 38-kDa RNA-binding proteins are present in cytoplasmic extracts, prepared from neuronal cells, and in isolated microtubule preparations. Our results support a novel model in which cis-acting signals, together with RNA-binding proteins are involved in the targeting of tau mRNA, that may ultimately lead to its axonal localization.
tau微管相关蛋白是一种主要在轴突中发现的神经元特异性蛋白，且受发育调控。tau的功能是稳定微管，这对于建立和维持神经元形态很重要。tau的轴突定位涉及一个多步骤过程，该过程在分化的原代神经元培养中进行研究。第一步涉及将其编码mRNA分选并亚细胞定位到轴突的近端部分。通过对神经元细胞进行转染试验，我们证明位于3'非翻译区的序列包含一个顺式作用信号，该信号参与tau mRNA的靶向定位。此外，使用紫外线交联试验，鉴定出了两种分子量分别为43 kDa和38 kDa的RNA结合蛋白，它们与位于同一功能区内的91个核苷酸的最小序列表现出特异性结合，该序列参与靶向定位。43 kDa和38 kDa的RNA结合蛋白存在于从神经元细胞制备的细胞质提取物以及分离的微管制剂中。我们的结果支持了一种新模型，即顺式作用信号与RNA结合蛋白一起参与tau mRNA的靶向定位，这最终可能导致其轴突定位。
