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bioRxiv · 10.1101/2025.02.09.637126

Calcium channel-coupled transcription factors facilitate direct nuclear signaling

Rao, E. R.·Thaxton, T.·Gama, E.·Godfrey, J.·Wei, C.·Lin, Q.·Li, Y.·Pastor, D. P. H.·Hansel, C.·Du, X.·Gomez, C. M.
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Abstract

VGCCs play crucial roles within the CNS, in maintaining cell excitability, enabling activity- dependent neuronal development, and forming long-term memory by regulating Ca2+ influx. The intracellular carboxyl-terminal domains of VGCC 1 subunits help regulate VGCC function. Emerging evidence suggests that some VGCC C-termini have functions independent of channel gating and exist as stable proteins. Here, we demonstrate that all VGCC gene family members express bicistronic mRNA transcripts that produce functionally distinct C-terminal proteins (CTPs) in tandem with full-length VGCC 1 subunits. Two of these CTPs, 1CCT and 1ACT, cycle to and from the nucleus in a Ca2+- and calmodulin-dependent fashion. 1CCT, 1ACT, and 1HCT regulate chromatin accessibility and/or bind directly to genes, regulating gene networks involved in neuronal differentiation and synaptic function in a Ca2+-dependent manner. This study elucidates a conserved process of coordinated protein expression within the VGCC family, coupling the channel function with VGCC C-terminal transcription factors.

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Rao, E. R., Thaxton, T., Gama, E., Godfrey, J., Wei, C., Lin, Q., Li, Y., Pastor, D. P. H., Hansel, C., Du, X., Gomez, C. M.. 2025-02-10. Calcium channel-coupled transcription factors facilitate direct nuclear signaling. https://doi.org/10.1101/2025.02.09.637126

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