Differential dissociation of G protein heterotrimers
Differential dissociation of G protein heterotrimers
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DOI：
10.1113/jphysiol.2008.153965
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发表时间：
2008-07-15
影响因子：
5.5
通讯作者：
Lambert, Nevin A.
中科院分区：
文献类型：
--
作者：
Digby, Gregory J.;Sethi, Pooja R.;Lambert, Nevin A.
异源三聚体G蛋白的信号传导通常是同种型特异性的，这意味着某些效应物仅由一个异源三聚体家族调节。例如，在可兴奋细胞中，内向整流钾（GIRK）通道被特异性地衍生自G（i/o）异源三聚体的G β γ二聚体激活。由于所有活性异源三聚体都被认为解离并释放游离的G β γ二聚体，因此尚不清楚为什么这些通道主要响应于G（i/o）异源三聚体释放的二聚体。我们在细胞中重建了GIRK通道激活，在细胞中我们可以定量质膜上的异源三聚体表达、GIRK通道激活和异源三聚体解离。我们发现，G（oA）异源三聚体比G（s）异源三聚体更有效的GIRK通道的激活剂时，每一个可比较的量。我们还发现活性G（oA）异源三聚体比活性G（s）异源三聚体更容易解离。因此，差异解离可以为GIRK通道和其他G β γ敏感效应器的G α特异性激活提供简单的解释。
Signalling by heterotrimeric G proteins is often isoform-specific, meaning certain effectors are regulated exclusively by one family of heterotrimers. For example, in excitable cells inwardly rectifying potassium (GIRK) channels are activated by G beta gamma dimers derived specifically from G(i/o) heterotrimers. Since all active heterotrimers are thought to dissociate and release free G beta gamma dimers, it is unclear why these channels respond primarily to dimers released by G(i/o) heterotrimers. We reconstituted GIRK channel activation in cells where we could quantify heterotrimer expression at the plasma membrane, GIRK channel activation, and heterotrimer dissociation. We find that G(oA) heterotrimers are more effective activators of GIRK channels than G(s) heterotrimers when comparable amounts of each are available. We also find that active G(oA) heterotrimers dissociate more readily than active G(s) heterotrimers. Differential dissociation may thus provide a simple explanation for G alpha-specific activation of GIRK channels and other G beta gamma-sensitive effectors.