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Regulation of tubulin, Tau and microtubule associated protein 2 expression during mouse brain development
C Charrière-Bertrand1, J Nunez
1INSERM U 282, Hôpital Henri Mondor, Crétail, France.
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.
Insights
Mouse brain development involves complex regulation of microtubule proteins like tubulin and Tau. Protein levels are controlled by both gene expression and post-translational modifications, impacting neuronal development.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Microtubule proteins, including tubulin, Tau, and MAP2, are crucial for neuronal structure and function.
- Understanding the regulation of these proteins during brain development is essential for comprehending neuronal maturation.
Purpose of the Study:
- To investigate the developmental regulation of tubulin, Tau, and MAP2 mRNA and protein levels in the mouse brain.
- To elucidate the mechanisms, including transcriptional and post-translational regulation, controlling microtubule protein expression during postnatal development.
Main Methods:
- Quantitative analysis of tubulin, Tau, and MAP2 mRNA and protein levels at different postnatal stages (3 days and adulthood).
- In vitro transcription assays using isolated nuclei to assess transcriptional activity.
- Comparison of in vivo mRNA levels with in vitro transcription rates to infer post-transcriptional regulation.
Main Results:
- Tubulin and Tau mRNA levels decreased by 85%, while their protein levels decreased by 50% from early development to adulthood.
- In vitro transcription showed minor variations for tubulin and Tau, suggesting post-transcriptional regulation (mRNA stability) contributes to decreased mRNA levels.
- MAP2 mRNA levels remained constant, but its protein level increased, indicating post-translational stabilization.
Conclusions:
- Microtubule protein expression during mouse brain development is regulated by a combination of transcriptional and post-translational mechanisms.
- Post-transcriptional regulation, particularly mRNA stability, plays a significant role in the developmental decrease of tubulin and Tau.
- MAP2 protein accumulation is primarily mediated by post-translational stabilization, independent of mRNA levels.