Pizzi M, Valerio A, Belloni M, Arrighi V, Alberici A, Liberini P, Spano P, Memo M
Department of Biomedical Sciences and Biotechnologies, University of Brescia, Italy.
Brain Res Mol Brain Res. 1995 Dec 1;34(1):38-44. doi: 10.1016/0169-328x(95)00129-g.
The molecular mechanism(s) responsible for the differential expression of various tau protein isoforms as well as their functional role in morphogenesis, neurofibrillary tangle formation and neurodegeneration have not been completely clarified. We found that the expression of tau proteins in primary cultures of cerebellar granule cells from neonatal rat brain is a developmentally regulated process affecting tau synthesis at different levels. Changes in tau RNA splicing are clearly demonstrated by PCR data showing the switching on of the mRNA containing four internal repeats by DIV 6 and the switching off of the mRNA containing three internal repeats after DIV 12. The changes in mRNA levels of the different tau isoforms during development in vitro occur in parallel with changes in tau protein expression, both qualitatively and quantitatively, as shown by Western analysis of protein extracts from granule cells at different DIV with an anti-tau polyclonal antibody. Finally, as indicated by MAP2 and tau immunocytochemistry data, the switch in tau protein expression appears to be contemporary with neurite outgrowth and cell differentiation. Our data suggest that a differential expression of various tau proteins parallels the degree of cell maturation.
导致各种tau蛋白异构体差异表达的分子机制及其在形态发生、神经原纤维缠结形成和神经退行性变中的功能作用尚未完全阐明。我们发现，新生大鼠脑小脑颗粒细胞原代培养物中tau蛋白的表达是一个受发育调控的过程，在不同水平上影响tau的合成。PCR数据清楚地表明了tau RNA剪接的变化，显示含四个内部重复序列的mRNA在第6天开始表达，而含三个内部重复序列的mRNA在第12天后停止表达。体外发育过程中不同tau异构体mRNA水平的变化与tau蛋白表达的变化在质量和数量上均平行，这通过用抗tau多克隆抗体对不同培养天数的颗粒细胞蛋白提取物进行Western分析得以显示。最后，正如MAP2和tau免疫细胞化学数据所示，tau蛋白表达的转变似乎与神经突生长和细胞分化同步。我们的数据表明，各种tau蛋白的差异表达与细胞成熟程度平行。
