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Functional and direct interaction between the RNA binding protein HuD and active Akt1
Toshinobu Fujiwara1, Akira Fukao, Yumi Sasano
1Laboratory of Disease Biology, Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. tosinobu@bikaken.or.jp
Nucleic Acids Research
|November 15, 2011
Summary
The RNA-binding protein HuD interacts with Akt1, crucial for neurite outgrowth and neuronal development. This interaction facilitates Akt1 recruitment, enhancing translation of key developmental proteins.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- The RNA-binding protein HuD is vital for neuronal development and plasticity.
- HuD enhances translation, with its linker region and poly(A) binding domain being critical for this function and neurite outgrowth.
Purpose of the Study:
- To explore the molecular interactions of HuD, specifically its interaction with Akt1.
- To elucidate the role of the HuD-Akt1 interaction in neurite outgrowth and translation regulation.
Main Methods:
- Investigated direct interaction between HuD and active Akt1 using biochemical assays.
- Utilized chimeric mutants of HuD and HuR to identify the critical region for Akt1 interaction.
- Employed a dominant-negative Akt1 mutant to assess the functional importance of the HuD-Akt1 interaction in PC12 cells.
Main Results:
- HuD, but not HuR, directly interacts with active Akt1.
- The linker region of HuD is essential for its interaction with Akt1.
- The HuD-Akt1 interaction is functionally required for Akt1-induced neurite outgrowth in PC12 cells.
Conclusions:
- RNA-bound HuD acts as an adapter protein, recruiting Akt1 to initiate neurite outgrowth.
- This mechanism may explain how HuD promotes the translation of mRNAs involved in neuronal development.
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