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

Voltage-dependent calcium (Ca super(2+)) 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 Ca super(2+) c...

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Bibliographic Details
Published in:Nature (London) 2001-06, Vol.411 (6838), p.701-706
Main Authors: Beguin, P, Nagashima, K, Gonoi, T, Shibasaki, T, Takahashi, K, Kashima, Y, Ozaki, N, Geering, K, Iwanaga, T, Seino, S
Format: Article
Language:English
Subjects:
AGem protein
AKir protein
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Summary:Voltage-dependent calcium (Ca super(2+)) 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 Ca super(2+) 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 Ca super(2+) channel activities by interacting directly with the beta -subunit. The reduced channel activities are due to a decrease in alpha sub(1)-subunit expression at the plasma membrane. The binding of Ca super(2+)/CaM to kir/Gem is required for this inhibitory effect by promoting the cytoplasmic localization of kir/Gem. Inhibition of L-type Ca super(2+) channels by kir/Gem prevents Ca super(2+)-triggered exocytosis in hormone-secreting cells. We propose that the small G-protein kir/Gem, interacting with beta -subunits, regulates Ca super(2+) channel expression at the cell surface.
ISSN:0028-0836
DOI:10.1038/35079621