Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression.
| dc.contributor.author | Li, Boxing | |
| dc.contributor.author | Tadross, Michael R | |
| dc.contributor.author | Tsien, Richard W | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2017-09-19T16:17:31Z | |
| dc.date.available | 2017-09-19T16:17:31Z | |
| dc.date.issued | 2016-02-19 | |
| dc.description.abstract | Voltage-gated CaV1.2 channels (L-type calcium channel α1C subunits) are critical mediators of transcription-dependent neural plasticity. Whether these channels signal via the influx of calcium ion (Ca(2+)), voltage-dependent conformational change (VΔC), or a combination of the two has thus far been equivocal. We fused CaV1.2 to a ligand-gated Ca(2+)-permeable channel, enabling independent control of localized Ca(2+) and VΔC signals. This revealed an unexpected dual requirement: Ca(2+) must first mobilize actin-bound Ca(2+)/calmodulin-dependent protein kinase II, freeing it for subsequent VΔC-mediated accumulation. Neither signal alone sufficed to activate transcription. Signal order was crucial: Efficiency peaked when Ca(2+) preceded VΔC by 10 to 20 seconds. CaV1.2 VΔC synergistically augmented signaling by N-methyl-d-aspartate receptors. Furthermore, VΔC mistuning correlated with autistic symptoms in Timothy syndrome. Thus, nonionic VΔC signaling is vital to the function of CaV1.2 in synaptic and neuropsychiatric processes. | |
| dc.identifier | ||
| dc.identifier | 351/6275/863 | |
| dc.identifier.eissn | 1095-9203 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | American Association for the Advancement of Science (AAAS) | |
| dc.relation.ispartof | Science | |
| dc.relation.isversionof | 10.1126/science.aad3647 | |
| dc.subject | Animals | |
| dc.subject | Autistic Disorder | |
| dc.subject | Calcium Channel Blockers | |
| dc.subject | Calcium Channels, L-Type | |
| dc.subject | Calcium Signaling | |
| dc.subject | Calcium-Calmodulin-Dependent Protein Kinase Type 2 | |
| dc.subject | Cells, Cultured | |
| dc.subject | Cyclic AMP Response Element-Binding Protein | |
| dc.subject | Gene Expression Regulation | |
| dc.subject | HEK293 Cells | |
| dc.subject | Hippocampus | |
| dc.subject | Humans | |
| dc.subject | Long QT Syndrome | |
| dc.subject | Neuronal Plasticity | |
| dc.subject | Neurons | |
| dc.subject | Nimodipine | |
| dc.subject | Protein Conformation | |
| dc.subject | Rats | |
| dc.subject | Rats, Sprague-Dawley | |
| dc.subject | Receptors, N-Methyl-D-Aspartate | |
| dc.subject | Synapses | |
| dc.subject | Syndactyly | |
| dc.title | Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Tadross, Michael R|0000-0002-7752-6380 | |
| pubs.author-url | ||
| pubs.begin-page | 863 | |
| pubs.end-page | 867 | |
| pubs.issue | 6275 | |
| pubs.organisational-group | Biomedical Engineering | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Pratt School of Engineering | |
| pubs.publication-status | Published | |
| pubs.volume | 351 |
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