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小鼠脑发育过程中微管蛋白、Tau蛋白和微管相关蛋白2表达的调控

Regulation of tubulin, Tau and microtubule associated protein 2 expression during mouse brain development.

作者信息

Charrière-Bertrand C, Nunez J

机构信息

INSERM U 282, Hôpital Henri Mondor, Crétail, France.

出版信息

Neurochem Int. 1992 Dec;21(4):535-41. doi: 10.1016/0197-0186(92)90085-6.

DOI:10.1016/0197-0186(92)90085-6
PMID:1303735
Abstract

The level of three microtubule proteins, tubulin, Tau and MAP2 and of their encoding mRNA was studied in the mouse brain at an early developmental stage (3 days postnatal) and in adulthood. The level of the mRNA encoding both tubulin and Tau decreased by 85% between these two stages whereas the encoded proteins decreased only by 50% during the same period. Thus, the level of these proteins seems to be regulated both negatively and positively by transcriptional and post translational mechanisms. In vitro transcription assays, performed with nuclei isolated at different postnatal stages, showed that the tubulin and Tau transcripts are produced with some variations during mouse brain development. However these fluctuations are much less important than the drops of the steady state levels of tubulin and Tau mRNA seen in vivo. Thus, the decrease in transcripts levels does not seem to result from reduced transcriptional activities, and can be ascribed to changes in mRNA stability occurring during brain development, i.e. to a post transcriptional mechanism. The situation is even more complex for MAP2: its encoding mRNA level remains constant during development whereas the in vitro transcription activity decreases markedly during the same period. Finally, MAP2 protein level increases during development although its encoding mRNA level remains constant suggesting that this protein is stabilized by a post translational mechanism.

摘要

在小鼠脑发育早期(出生后3天)及成年期,对三种微管蛋白(微管蛋白、Tau蛋白和微管相关蛋白2(MAP2))及其编码mRNA的水平进行了研究。在这两个阶段之间,微管蛋白和Tau蛋白编码mRNA的水平下降了85%,而在此期间,编码蛋白仅下降了50%。因此,这些蛋白质的水平似乎受到转录和翻译后机制的正负调控。对在不同出生后阶段分离的细胞核进行的体外转录分析表明,在小鼠脑发育过程中,微管蛋白和Tau转录本的产生存在一些差异。然而,这些波动远不如在体内观察到的微管蛋白和Tau mRNA稳态水平的下降那么显著。因此,转录本水平的下降似乎并非源于转录活性的降低,而可归因于脑发育过程中mRNA稳定性的变化,即转录后机制。对于MAP2而言,情况更为复杂:其编码mRNA水平在发育过程中保持恒定,而同期体外转录活性则显著下降。最后,MAP2蛋白水平在发育过程中升高,尽管其编码mRNA水平保持恒定,这表明该蛋白是通过翻译后机制稳定的。

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