β-Subunit of the voltage-gated Ca <sup>2+</sup> channel Cav1.2 drives signaling to the nucleus via H-Ras

Significance The L-type voltage-gated calcium channel Cav1.2 mediates depolarization-triggered signaling cascades that regulate neuronal-specific transcription factors such as CREB and immediate-early genes. We demonstrate that the interaction of the intracellular β-subunit of the channel with H-Ras is indispensable for depolarization-triggered gene activation. The binding of the recombinant β-subunit to H-Ras and H-Ras pulldown assays confirms the ability of H-Ras to physically interact with the β-subunit. We show that gene transcription also requires the binding of Ca 2+ to the channel pore and is calcium-influx independent. These results delineate Cav1.2–H-Ras interaction by extracellular signaling as a mode of rapid induction of gene transcription. They expand the repertoire of Cav1.2 metabotropic signaling triggered by depolarization-induced conformational changes, which require channel-pore occupancy and are calcium-influx independent.

β-Subunit of the voltage-gated Ca ²⁺ channel Cav1.2 drives signaling to the nucleus via H-Ras Journal Articles