Regulation of rod photoreceptor function by farnesylated G-protein γ-subunits.
Regulation of rod photoreceptor function by farnesylated G-protein γ-subunits.
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DOI：
10.1371/journal.pone.0272506
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
异源三聚体G蛋白转导素（Gt）是视网膜视杆细胞和视锥细胞中的关键信号转导和放大因子。尽管它们的Gγ亚基具有相似的亚基组成、相似的氨基酸同一性和相同的翻译后法尼基化，但视杆细胞和视锥细胞分别依赖于独特的Gγ1（Gngt1）和Gγc（Gngt2）同种型。唯一的另一个法尼基化的G蛋白γ亚基Gγ11（Gng11）在多种组织中表达，但不在视网膜中表达。为了确定Gγ1是否独特地调节视杆细胞光转导，我们在Gγ1缺陷小鼠中产生了表达Gγ1、Gγc或Gγ11的转基因视杆细胞，并分析了它们的特性。免疫组织化学和Western印迹证实了每个转基因Gγ在视杆细胞中的稳健表达和Gαt1表达的恢复，G αt1表达在Gγ1缺陷的视杆中大大降低。视网膜电图显示所有三个转基因Gγ1缺陷系的视觉功能均得到恢复。从单个转基因视杆的记录表明，Gγ1缺陷视杆中受损的光敏性也完全恢复。在所有暗适应转基因株系中，Gαt1靶向于外节，逆转了其在Gγ1缺陷型视杆中发现的弥散定位。在所有三个转基因株系中，强光照射均能诱导Gαt1从视杆外节向内节易位。然而，Gγ11转基因小鼠的Gαt1易位发生在显著较暗的背景光下。与此一致，经视网膜ERG记录显示，Gγ11转基因小鼠在中等背景照明下的反应逐渐恢复，但Gγ1对照小鼠没有。因此，虽然法尼基化的Gγ亚基在支持视杆细胞光转导方面具有功能活性并且在很大程度上是可互换的，但普遍存在的Gγ11对视网膜特异性Gγ亚型的替代会影响视杆细胞适应背景光的能力。
Heterotrimeric G-protein transducin, Gt, is a key signal transducer and amplifier in retinal rod and cone photoreceptor cells. Despite similar subunit composition, close amino acid identity, and identical posttranslational farnesylation of their Gγ subunits, rods and cones rely on unique Gγ1 (Gngt1) and Gγc (Gngt2) isoforms, respectively. The only other farnesylated G-protein γ-subunit, Gγ11 (Gng11), is expressed in multiple tissues but not retina. To determine whether Gγ1 regulates uniquely rod phototransduction, we generated transgenic rods expressing Gγ1, Gγc, or Gγ11 in Gγ1-deficient mice and analyzed their properties. Immunohistochemistry and Western blotting demonstrated the robust expression of each transgenic Gγ in rod cells and restoration of Gαt1 expression, which is greatly reduced in Gγ1-deficient rods. Electroretinography showed restoration of visual function in all three transgenic Gγ1-deficient lines. Recordings from individual transgenic rods showed that photosensitivity impaired in Gγ1-deficient rods was also fully restored. In all dark-adapted transgenic lines, Gαt1 was targeted to the outer segments, reversing its diffuse localization found in Gγ1-deficient rods. Bright illumination triggered Gαt1 translocation from the rod outer to inner segments in all three transgenic strains. However, Gαt1 translocation in Gγ11 transgenic mice occurred at significantly dimmer background light. Consistent with this, transretinal ERG recordings revealed gradual response recovery in moderate background illumination in Gγ11 transgenic mice but not in Gγ1 controls. Thus, while farnesylated Gγ subunits are functionally active and largely interchangeable in supporting rod phototransduction, replacement of retina-specific Gγ isoforms by the ubiquitous Gγ11 affects the ability of rods to adapt to background light.
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影响因子：
3.4
作者：
Dexter PM;Lobanova ES;Finkelstein S;Spencer WJ;Skiba NP;Arshavsky VY
通讯作者：
Arshavsky VY
影响因子：
1.2
作者：
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通讯作者：
Robishaw, Janet D.
影响因子：
5.5
作者：
Chen, C. -K.;Woodruff, M. L.;Fain, G. L.
通讯作者：
Fain, G. L.
影响因子：
5.3
作者：
Frederiksen, Rikard;Morshedian, Ala;Sampath, Alapakkam P.
通讯作者：
Sampath, Alapakkam P.
影响因子：
4.8
作者：
Krumins, AM;Gilman, AG
通讯作者：
Gilman, AG