@article {47315,
	title = {Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression.},
	journal = {Science (New York, N.Y.)},
	volume = {351},
	year = {2016},
	month = {2016 Feb 19},
	pages = {863-7},
	abstract = {<p>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 (Ca2+), voltage-dependent conformational change (VΔC), or a combination of the two has thus far been equivocal. We fused CaV1.2 to a ligand-gated Ca2+-permeable channel, enabling independent control of localized Ca2+\&nbsp;and VΔC signals. This revealed an unexpected dual requirement: Ca2+\&nbsp;must first mobilize actin-bound Ca2+/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 Ca2+\&nbsp;preceded VΔC by 10 to 20 seconds. CaV1.2 VΔC synergistically augmented signaling by\&nbsp;<em>N</em>-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.</p>
},
	doi = {10.1126/science.aad3647},
	author = {Li, Boxing and Tadross, Michael R and Tsien, Richard W}
}
