Modulation of Ca v3.1 T-type Ca 2+ channels by the ran binding protein RanBPM

Abstract

In order to study the currently unknown cellular signaling pathways of Ca v3.1 T-type Ca 2+ channels (Ca v3.1 channels), we performed a yeast two-hybrid screening using intracellular domains of Ca v3.1 α1 subunit as bait. After screening the human brain cDNA library, several proteins, including RanBPM, were identified as interacting with Ca v3.1 channels. RanBPM was found to bind to the cytoplasmic intracellular loop between transmembrane domains I and II of Ca v3.1 channels. Using whole-cell patch-clamp techniques, we found that Ca v3.1 currents were increased by the expression of RanBPM in HEK293/Ca v3.1 cells. We next examined whether RanBPM affected the biophysical properties and plasma membrane expression of Ca v3.1 channels. Furthermore, we showed that the PKC activator inhibited Ca v3.1 currents, an effect that was abolished by the expression of RanBPM. These results suggest that RanBPM could be a key regulator of Ca v3.1 channel-mediated signaling pathways.