Farnesylation of retinal transducin underlies its translocation during light adaptation

Farnesylation of retinal transducin underlies its translocation during light adaptation
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DOI:
10.1016/j.neuron.2005.07.025
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发表时间:
2005-08-18
期刊:
影响因子:
16.2
通讯作者:
Fukada, Y
Fukada, Y
中科院分区:
医学1区
文献类型:
--
作者:
Kassai, H;Aiba, A;Fukada, Y

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G蛋白通过异戊二烯化进行后修饰:法尼基化或香叶基香叶基化。视网膜转导素的γ亚基(T α/T β γ)被选择性地法尼基化,并且法尼基化是视杆细胞中转导素介导的光信号传导所需的。然而,这种选择性异戊二烯化是否以及如何调节细胞功能仍然知之甚少。在这里,我们报告说,敲入小鼠表达geranylgeranylated T γ表现出正常的杆反应暗适应条件下的闪光灯,但在光适应表现出受损的属性。值得注意的是,T γ的香叶基香叶基化抑制了光诱导的T β γ从膜到胞质溶胶的转变,并且还减弱了其从外节到内区的光依赖性易位,这是一种有助于视网膜光适应的事件。这些结果表明,虽然法尼基化的转导是可互换的香叶基香叶基的光信号,选择性法尼基化是重要的视觉灵敏度调节,通过提供足够的,但不是过度的膜锚定的T β γ。
G proteins are posttranslationally modified by isoprenylation: either farnesylation or geranylgeranylation. The gamma subunit of retinal transducin (T alpha/T beta gamma) is selectively farnesylated, and the farnesylation is required for light signaling mediated by transducin in rod cells. However, whether and how this selective isoprenylation regulates cellular functions remain poorly understood. Here we report that knockin mice expressing geranylgeranylated T gamma showed normal rod responses to dim flashes under dark-adapted conditions but exhibited impaired properties in light adaptation. Of note, geranylgeranylation of T gamma suppressed light-induced transition of T beta gamma from membrane to cytosol, and also attenuated its light-dependent translocation from the outer segment to the inner region, an event contributing to retinal light adaptation. These results indicate that, while the farnesylation of transducin is interchangeable with the geranylgeranylation in terms of the light signaling, the selective farnesylation is important for visual sensitivity regulation by providing sufficient but not excessive membrane anchoring of T beta gamma.