β-Subunit of the voltage-gated Ca²⁺ channel Cav1.2 drives signaling to the nucleus via H-Ras.

ABSTRACT: Depolarization-induced signaling to the nucleus by the L-type voltage-gated calcium channel Cav1.2 is widely assumed to proceed by elevating intracellular calcium. The apparent lack of quantitative correlation between Ca²⁺ influx and gene activation suggests an alternative activation pathway. Here, we demonstrate that membrane depolarization of HEK293 cells transfected with α₁1.2/β2b/α2δ subunits (Cav1.2) triggers c-Fos and MeCP2 activation via the Ras/ERK/CREB pathway. Nuclear signaling is lost either by absence of the intracellular β2 subunit or by transfecting the cells with the channel mutant α₁1.2^W440A/β2b/α2δ, a mutation that disrupts the interaction between α₁1.2 and β2 subunits. Pulldown assays in neuronal SH-SY5Y cells and in

SUBMITTER: Servili E 

PROVIDER: S-EPMC6140482 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature