Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression.

janelia7_blocks-janelia7_biblio_header | block

Science (New York, N.Y.). 2016 Feb 19;351(6275):863-7. doi: 10.1126/science.aad3647

Li B, Tadross MR, Tsien RW

janelia7_blocks-janelia7_biblio_abstract | block

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 (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+ and VΔC signals. This revealed an unexpected dual requirement: Ca2+ 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+ 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.

node:body | entity_field

Main Menu (Mobile)- Block

Main Menu - Block

Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression.

Abstract

Janelia Authors