Modulation of Ca(v)3.1 T-type Ca2+ channels by the ran binding protein RanBPM.
In order to study the currently unknown cellular signaling pathways of Ca(v)3.1 T-type Ca(2+) channels (Ca(v)3.1 channels), we performed a yeast two-hybrid screening using intracellular domains of Ca(v)3.1 alpha1 subunit as bait. After screening the human brain cDNA library, several proteins, including RanBPM, were identified as interacting with Ca(v)3.1 channels. RanBPM was found to bind to the cytoplasmic intracellular loop between transmembrane domains I and II of Ca(v)3.1 channels. Using whole-cell patch-clamp techniques, we found that Ca(v)3.1 currents were increased by the expression of RanBPM in HEK293/Ca(v)3.1 cells. We next examined whether RanBPM affected the biophysical properties and plasma membrane expression of Ca(v)3.1 channels. Furthermore, we showed that the PKC activator inhibited Ca(v)3.1 currents, an effect that was abolished by the expression of RanBPM. These results suggest that RanBPM could be a key regulator of Ca(v)3.1 channel-mediated signaling pathways.
Kim
Taehyun
T
Life Sciences Division, Korea Institute of Science and Technology, 39-1 Hawholgok-dong Sunbuk-gu, Seoul 136-791, Republic of Korea.
Kim
Sunoh
S
Yun
Hyung-Mun
HM
Chung
Kwang Chul
KC
Han
Ye Sun
YS
Shin
Hee-Sup
HS
Rhim
Hyewhon
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D006801:Humans; D008564:Membrane Potentials; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; C121855:CACNA1G protein, human; D020747:Calcium Channels, T-Type; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9; D011493:Protein Kinase C