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Published on: July 10, 2018
Up-regulation of dendritic Kv4.2 mRNA by activation of the NMDA receptor
1Department of Medicine and Microbiology, College of Medicine, Signaling Disorder Research Center, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Abstract:
The localization of Kv4.2 mRNAs in dendritic regions suggests that Kv4.2 channels, which originate from on-site protein synthesis in the dendrites, might play a role in synaptic function. In this study, we determined the molecular mechanisms of dendritic transport of Kv4.2 mRNA. Three hours of incubation following a brief depolarization resulted in significant increases in Kv4.2 mRNA levels in both cell bodies and dendrites. The increase in the mRNA in the dendrites was mediated by transcription- and translation-independent mechanisms. In order to further clarify the molecular mechanism of dendritic transport of Kv4.2 mRNA, we used the GFP-MS2 reporting system. Consistent with the in situ data, depolarization resulted in significant increases in dendritic levels of Kv4.2 mRNA at the maximal length at which Kv4.2 mRNA could be detected. These increases were mediated in a synaptic NMDA receptor- and Ca(2+)-dependent fashion. Collectively, these results indicate that Kv4.2 mRNA levels are regulated in response to synaptic activity, and this phenomenon may be the mechanism underlying the homeostasis of Kv4.2 protein on dendritic surfaces.
Insights
Synaptic activity regulates Kv4.2 mRNA transport to dendrites via NMDA receptors and calcium. This process is crucial for maintaining Kv4.2 protein levels at the synapse.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Kv4.2 channels are located in dendrites, suggesting local protein synthesis.
- On-site synthesis implies dendritic transport of Kv4.2 mRNA is vital for synaptic function.
Purpose of the Study:
- To elucidate the molecular mechanisms governing the dendritic transport of Kv4.2 mRNA.
- To investigate how synaptic activity influences Kv4.2 mRNA localization in neurons.
Main Methods:
- Utilized the GFP-MS2 reporting system to track Kv4.2 mRNA.
- Applied brief depolarization and measured mRNA levels in cell bodies and dendrites.
- Investigated the role of NMDA receptors and Ca(2+) in mRNA transport.
Main Results:
- Depolarization increased Kv4.2 mRNA in both cell bodies and dendrites.
- Dendritic mRNA increase was transcription- and translation-independent.
- NMDA receptor and Ca(2+) signaling mediated depolarization-induced dendritic Kv4.2 mRNA increases.
Conclusions:
- Kv4.2 mRNA levels are dynamically regulated by synaptic activity.
- This regulation is dependent on NMDA receptor and Ca(2+) signaling pathways.
- Activity-dependent dendritic transport of Kv4.2 mRNA may ensure Kv4.2 protein homeostasis at dendritic surfaces.
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