Cytosolic peptides encoding CaV1 C-termini downregulate the calcium channel activity-neuritogenesis coupling
Yaxiong Yang1,2, Zhen Yu1,2, Jinli Geng1,2
1Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, School of Engineering Medicine, Beihang University, Beijing, 100083, China.
Communications Biology
|May 19, 2022
Summary
Cytosolic CaV1 DCT peptides inhibit neurite outgrowth by interacting with CaV1 channels. This inhibition is dependent on peptide affinity and localization, indirectly promoting neuritogenesis via nuclear retention.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- L-type Ca2+ (CaV1) channels are crucial for neuritogenesis.
- CaV1 DCT peptides can function as nuclear transcription factors promoting neuritogenesis.
Purpose of the Study:
- Investigate the role of cytosolic CaV1 DCT peptides in neuritogenesis.
- Determine the mechanism by which cytosolic DCT peptides affect CaV1 channel activity and neuronal morphology.
Main Methods:
- Utilized exemplary CaV1.3 channels and cortical neurons.
- Analyzed interactions between cytosolic DCT peptides and CaV1 channels.
- Assessed effects on Ca2+ influx, neurite outgrowth, CREB activation, and c-Fos expression.
Main Results:
- Cytosolic DCT peptides downregulate neurite outgrowth via interaction with the CaV1 apo-calmodulin binding motif.
- Inhibition of CaV1 channel activity and neurite extension is quantitatively correlated with DCT binding affinity.
- Cytosolic inhibition indirectly promotes neuritogenesis by enhancing Ca2+-sensitive nuclear retention of DCT.
Conclusions:
- DCT peptides act as CaV1 inhibitors, regulating channel activity-neuritogenesis coupling.
- The effects of DCT peptides are variant-, affinity-, and localization-dependent.
- Cytosolic DCT peptides exhibit a distinct regulatory role compared to nuclear DCT peptides.
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