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Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus.

Authors: Ch'ng, TH  Uzgil, B  Lin, P  Avliyakulov, NK  O'Dell, TJ  Martin, KC 
Citation: Ch'ng TH, etal., Cell. 2012 Jul 6;150(1):207-21. doi: 10.1016/j.cell.2012.05.027.
Pubmed: (View Article at PubMed) PMID:22770221
DOI: Full-text: DOI:10.1016/j.cell.2012.05.027

Long-lasting changes in synaptic efficacy, such as those underlying long-term memory, require transcription. Activity-dependent transport of synaptically localized transcriptional regulators provides a direct means of coupling synaptic stimulation with changes in transcription. The CREB-regulated transcriptional coactivator (CRTC1), which is required for long-term hippocampal plasticity, binds CREB to potently promote transcription. We show that CRTC1 localizes to synapses in silenced hippocampal neurons but translocates to the nucleus in response to localized synaptic stimulation. Regulated nuclear translocation occurs only in excitatory neurons and requires calcium influx and calcineurin activation. CRTC1 is controlled in a dual fashion with activity regulating CRTC1 nuclear translocation and cAMP modulating its persistence in the nucleus. Neuronal activity triggers a complex change in CRTC1 phosphorylation, suggesting that CRTC1 may link specific types of stimuli to specific changes in gene expression. Together, our results indicate that synapse-to-nuclear transport of CRTC1 dynamically informs the nucleus about synaptic activity.


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RGD Object Information
RGD ID: 9685164
Created: 2014-12-18
Species: All species
Last Modified: 2014-12-18
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.