Fast inactivation of a brain K+ channel composed of Kv1.1 and Kvβ1.1 subunits modulated by G protein βγ subunits
Fast inactivation of a brain K+ channel composed of Kv1.1 and Kvβ1.1 subunits modulated by G protein βγ subunits
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DOI：
10.1093/emboj/18.5.1245
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发表时间：
1999-03-01
期刊：
影响因子：
11.4
通讯作者：
Lotan, I
中科院分区：
文献类型：
--
作者：
Jing, J;Chikvashvili, D;Lotan, I
A型电压门控K+通道的调制可以引起神经元信号的可塑性变化。结果表明，延迟整流型K(V)1.1通道与K(V)β1.1亚基结合后可转化为A型通道，这种转化是部分的，并受磷酸化和微丝的调节。在非洲爪哇卵母细胞中，Gβ(1)γ(2)亚基的表达伴随着通道(由K(V)1.1和K(V)β1.1亚基组成)的表达，而不是在通道在质膜上表达之后，增加了通道向A型转化的程度。相反，通过共表达P-肾上腺素能受体激酶的C末端片段来清除内源性Gβ伽马可降低向A型转化的程度。Gβγ共表达的作用被二氢细胞松弛素B阻断，二氢细胞松弛素B是我们先前展示的一种微丝干扰剂，以增强向A型转化的程度，以及K(V)β1.1、Gβ(1)γ(2)亚基的过表达直接与K(V)1.1和K(V)β1.1的GST融合片段相互作用，Gβ(1)γ(2)的GO表达导致与K(V)1.1的共同免疫沉淀。因此，我们认为Gβ(1)γ(2)在通道组装过程中直接影响K(V)1.1和K(V)beta 1.1之间的相互作用，进而破坏通道与微丝相互作用的能力，导致A型转化的程度增加。
Modulation of A-type voltage-gated K+ channels can produce plastic changes in neuronal signaling. It was shown that the delayed-rectifier K(v)1.1 channel can be converted to A-type upon association with K(v)beta 1.1 subunits; the conversion is only partial and is modulated by phosphorylation and microfilaments, Here we show that, in Xenopus oocytes, expression of G beta(1)gamma(2) subunits concomitantly with the channel (composed of K(v)1.1 and K(v)beta 1.1 subunits), but not after the channel's expression in the plasma membrane, increases the extent of conversion to A-type. Conversely, scavenging endogenous G beta gamma by co-expression of the C-terminal fragment of the P-adrenergic receptor kinase reduces the extent of conversion to A-type. The effect of G beta gamma co-expression is occluded by treatment with dihydro-cytochalasin B, a microfilament-disrupting agent shown previously by us to enhance the extent of conversion to A-type, and by overexpression of K(v)beta 1.1, G beta(1)gamma(2) subunits interact directly with GST fusion fragments of K(v)1.1 and K(v)beta 1.1, Go-expression of G beta(1)gamma(2) causes co-immunoprecipitation with K(v)1.1 of more K(v)beta 1.1 subunits. Thus, we suggest that G beta(1)gamma(2) directly affects the interaction between K(v)1.1 and K(v)beta 1.1 during channel assembly which, in turn, disrupts the ability of the channel to interact with microfilaments, resulting in an increased extent of A-type conversion.