Key result
Cav1.2 β-subunit interaction with H-Ras drives depolarization-triggered gene activation via calcium binding rather than influx.
This study delineates a novel metabotropic signaling pathway for Cav1.2, showing that its β-subunit interacts with H-Ras to drive gene transcription independently of calcium influx.
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.
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Servili et al. (2018) studied this question. Cav1.2 β-subunit interaction with H-Ras was evaluated on Depolarization-triggered gene activation. The interaction of the intracellular β-subunit of the Cav1.2 channel with H-Ras is indispensable for depolarization-triggered gene activation, requiring Ca2+ binding but not calcium influx.
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