Modulation of Cav3.1 T-type Ca2+ channels by the ran binding protein RanBPM

In order to study the currently unknown cellular signaling pathways of Cav3.1 T-type Ca2+ channels (Cav3.1 channels), we performed a yeast two-hybrid screening using intracellular domains of Cav3.1 α1 subunit as bait. After screening the human brain cDNA library, several proteins, including RanBPM, were identified as interacting with Cav3.1 channels. RanBPM was found to bind to the cytoplasmic intracellular loop between transmembrane domains I and II of Cav3.1 channels. Using whole-cell patch-clamp techniques, we found that Cav3.1 currents were increased by the expression of RanBPM in HEK293/Cav3.1 cells. We next examined whether RanBPM affected the biophysical properties and plasma membrane expression of Cav3.1 channels. Furthermore, we showed that the PKC activator inhibited Cav3.1 currents, an effect that was abolished by the expression of RanBPM. These results suggest that RanBPM could be a key regulator of Cav3.1 channel-mediated signaling pathways.