Transducin β-Subunit Can Interact with Multiple G-Protein γ-Subunits to Enable Light Detection by Rod Photoreceptors.
Transducin β-Subunit Can Interact with Multiple G-Protein γ-Subunits to Enable Light Detection by Rod Photoreceptors.
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DOI：
10.1523/eneuro.0144-18.2018
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发表时间：
2018-05
期刊：
影响因子：
3.4
通讯作者：
Arshavsky VY
中科院分区：
文献类型：
--
作者：
Dexter PM;Lobanova ES;Finkelstein S;Spencer WJ;Skiba NP;Arshavsky VY
异三聚体G蛋白转导蛋白在脊椎动物光感受器细胞中介导视觉信号。转导蛋白功能的许多方面都是从缺乏单个亚基的基因敲除小鼠那里学到的。特别令人感兴趣的是它的杆状特异性γ亚基(Gγ1)的敲除。两项使用独立产生的小鼠的研究证明，这种敲除导致受影响杆的光敏感度显著降低60倍，但对剩余的α亚单位(Gαt)如何在没有其同源Gβ1γ1亚单位伙伴的情况下如何介导光传导提供了不同的解释。一项研究发现，光敏感度的降低与感光杆外节中Gαt含量的相应降低相匹配，并提出Gαt的激活是由剩余的Gβ1与其他在光感受器中自然表达的Gγ亚单位共同支持的。相反，第二项研究报告了相同的光敏性损失，但Gαt降低了很多，仅约六倍，并提出这些棒的光响应根本不需要Gβγ。为了解决这一争议，并阐明在Gγ1基因敲除棒中驱动视觉信号的机制，我们并排分析了这两个小鼠品系。我们首先确定两只小鼠的外节都有相同的Gαt含量，这比野生型(WT)水平的∼减少了65倍。我们进一步证明了剩余的Gβ1存在于含有内源性Gγ2和Gγ3亚基的复合体中，这些复合体也存在于野生型杆中。综上所述，这些结果反对Gαt单独支持Gγ1敲除棒的光反应的观点，并表明Gβ1γ1在介导脊椎动物光转导方面并不是唯一的。
The heterotrimeric G-protein transducin mediates visual signaling in vertebrate photoreceptor cells. Many aspects of the function of transducin were learned from knock-out mice lacking its individual subunits. Of particular interest is the knockout of its rod-specific γ-subunit (Gγ1). Two studies using independently generated mice documented that this knockout results in a considerable >60-fold reduction in the light sensitivity of affected rods, but provided different interpretations of how the remaining α-subunit (Gαt) mediates phototransduction without its cognate Gβ1γ1-subunit partner. One study found that the light sensitivity reduction matched a corresponding reduction in Gαt content in the light-sensing rod outer segments and proposed that Gαt activation is supported by remaining Gβ1 associating with other Gγ subunits naturally expressed in photoreceptors. In contrast, the second study reported the same light sensitivity loss but a much lower, only approximately sixfold, reduction of Gαt and proposed that the light responses of these rods do not require Gβγ at all. To resolve this controversy and elucidate the mechanism driving visual signaling in Gγ1 knock-out rods, we analyzed both mouse lines side by side. We first determined that the outer segments of both mice have identical Gαt content, which is reduced ∼65-fold from the wild-type (WT) level. We further demonstrated that the remaining Gβ1 is present in a complex with endogenous Gγ2 and Gγ3 subunits and that these complexes exist in wild-type rods as well. Together, these results argue against the idea that Gαt alone supports light responses of Gγ1 knock-out rods and suggest that Gβ1γ1 is not unique in its ability to mediate vertebrate phototransduction.