Regulation of Ca 2+ channel expression at the cell surface by the small G-protein kir/Gem

• Published in: Nature (London) 2001-06, Vol.411 (6838), p.701-706
• Main Authors: Geering, Käthi, Seino, Susumu, Béguin, Pascal, Iwanaga, Toshihiko, Takahashi, Kazuo, Ozaki, Nobuaki, Kashima, Yasushige, Gonoi, Tohru, Shibasaki, Tadao, Nagashima, Kazuaki
• Format: Article
• Language: English
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35079621

Voltage-dependent calcium (Ca2+) channels are involved in many specialized cellular functions, and are controlled by intracellular signals such as heterotrimeric G-proteins, protein kinases and calmodulin (CaM). However, the direct role of small G-proteins in the regulation of Ca2+ channels is unclear. We report here that the GTP-bound form of kir/Gem, identified originally as a Ras-related small G-protein that binds CaM, inhibits high-voltage-activated Ca2+ channel activities by interacting directly with the β-subunit. The reduced channel activities are due to a decrease in α1-subunit expression at the plasma membrane. The binding of Ca2+/CaM to kir/Gem is required for this inhibitory effect by promoting the cytoplasmic localization of kir/Gem. Inhibition of L-type Ca2+ channels by kir/Gem prevents Ca2+-triggered exocytosis in hormone-secreting cells. We propose that the small G-protein kir/Gem, interacting with β-subunits, regulates Ca2+ channel expression at the cell surface.