Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem.
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.
Béguin
P
P
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Nagashima
K
K
Gonoi
T
T
Shibasaki
T
T
Takahashi
K
K
Kashima
Y
Y
Ozaki
N
N
Geering
K
K
Iwanaga
T
T
Seino
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D051379:Mice; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014981:Xenopus
D015220:Calcium Channels; D017874:Immediate-Early Proteins; D007328:Insulin; D011993:Recombinant Fusion Proteins; D006160:Guanosine Triphosphate; C088119:Gem protein, mouse; D020559:Monomeric GTP-Binding Proteins; D002118:Calcium