Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem
Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem
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DOI：
10.1038/35079621
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发表时间：
2001-06-01
期刊：
影响因子：
64.8
通讯作者：
Seino, S
中科院分区：
文献类型：
--
作者：
Béguin, P;Nagashima, K;Seino, S
电压依赖性钙通道参与许多特殊的细胞功能(1-3)，并受细胞内异源三聚体G蛋白(4)、蛋白激酶(5，6)和钙调素(CaM)(7，8)等信号的控制。然而，小G蛋白在钙通道调节中的直接作用尚不清楚。我们在这里报道了KIR/Gem的GTP结合形式，最初被鉴定为与CaM9-11结合的RAS相关小G蛋白，通过直接与β-亚基相互作用抑制高压激活的钙通道活动。通道活性的降低是由于质膜上α(1)亚单位表达的减少。这种抑制作用需要钙/钙调素与KIR/Gem结合，促进KIR/Gem的胞质定位。KIR/GEM抑制L钙通道可阻止钙离子引起的激素分泌细胞胞吐。我们认为，小G蛋白kir/Gem与β-亚基相互作用，调节细胞表面钙通道的表达。
Voltage-dependent calcium (Ca2+) channels are involved in many specialized cellular functions(1-3), and are controlled by intracellular signals such as heterotrimeric G-proteins(4), protein kinases(5,6) and calmodulin (CaM)(7,8). 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 CaM9-11, inhibits high-voltage-activated Ca2+ channel activities by interacting directly with the beta -subunit. The reduced channel activities are due to a decrease in alpha (1)-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.