Title: Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem.

Authors: P Béguin, K Nagashima, T Gonoi, T Shibasaki, K Takahashi, Y Kashima, N Ozaki, K Geering, T Iwanaga, S Seino

Journal, date & volume: Nature, 2001 Jun 7 , 411, 701-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11395774

Abstract
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 beta-subunit. The reduced channel activities are due to a decrease in alpha1-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 beta-subunits, regulates Ca2+ channel expression at the cell surface.