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Updated: Jun 19, 2025
07:51
Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
25.3K
Calmodulin Triggers Activity-Dependent rRNA Biogenesis via Interaction with DDX21
Jia-Lin Yang1, Xue Sun1, Jun-Xiu Shi1
1Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China.
Summary
Calmodulin (CaM) links neuronal activity to protein synthesis by regulating ribosomal RNA (rRNA) biogenesis. This Ca2+-dependent process is crucial for synaptic plasticity and axon growth, with identified small molecules impacting this pathway.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Activity-dependent translation is vital for synaptic plasticity and memory.
- Signaling pathways connecting neuronal activity to translation are not fully understood.
Purpose of the Study:
- To elucidate the role of calmodulin (CaM) in activity-dependent ribosomal RNA (rRNA) biogenesis in neurons.
- To identify molecular mechanisms linking Ca2+ signaling to rRNA synthesis and protein production.
Main Methods:
- Investigated CaM's interaction with DDX21 in a Ca2+-dependent manner.
- Assessed the impact of CaM-DDX21 interaction on RPA194 liberation and rRNA transcription.
- Utilized high-throughput screening to identify small molecules affecting the CaM-DDX21 pathway.
Main Results:
- CaM regulates Ca2+-dependent rRNA synthesis, essential for protein synthesis and axon growth in hippocampal neurons.
- CaM interacts with DDX21, altering its conformation to release RPA194 for rDNA transcription.
- Batefenterol and indacaterol were identified to inhibit CaM-DDX21 interaction, suppressing rRNA synthesis and axon growth.
Conclusions:
- Calmodulin acts as a crucial messenger linking activity-induced Ca2+ influx to nucleolar events governing protein synthesis.
- This study reveals a novel role for CaM in transmitting neuronal stimulation signals to the nucleolus for regulating protein synthesis and neuronal growth.
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