Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.
Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.
复制标题
K296E 视蛋白对光转导的组成性激活并不是光感受器变性的原因。
DOI：
10.1073/pnas.92.8.3551
复制
发表时间：
1995
影响因子：
11.1
通讯作者：
Dryja,TP
中科院分区：
文献类型：
--
作者：
Li,T;Franson,WK;Gordon,JW;Berson,EL;Dryja,TP
视紫红质基因中的错义突变Lys-296-->Glu（K296 E）产生没有发色团结合位点的视蛋白，因此不被光激活。然而，突变体视蛋白在体外组成性激活transformin并在体内引起感光细胞变性，可能是通过连续激活光转导级联反应，类似于持续暴露于环境光。我们研究了K296 E突变在8个系列的转基因小鼠。每一行开发的光感受器退化与退化率单调增加的突变体：野生型视蛋白mRNA的比例增加。在任何时候，在变性过程中，有内源性光适应的视网膜电图测量。突变体视蛋白被发现总是磷酸化，并稳定地结合到arrestin。光非依赖性激活transducin后，证明只有去除抑制蛋白和K296 E视蛋白的去磷酸化。因此，K296 E视蛋白在体内不激活光转导级联，因为它被光感受器失活机制关闭。我们的数据表明，K296 E突变不会通过持续激活光转导引起感光细胞变性。
The missense mutation Lys-296-->Glu (K296E) in the rhodopsin gene produces an opsin with no chromophore binding site and therefore is not activated by light. Nevertheless, the mutant opsin constitutively activates transducin in vitro and causes photoreceptor degeneration in vivo, possibly by continuously activating the phototransduction cascade, analogous to constant exposure to environmental light. We studied the K296E mutation in eight lines of transgenic mice. Each line developed photoreceptor degeneration with the rate of degeneration increasing monotonically as the ratio of mutant:wild-type opsin mRNA increased. At no time in the course of degeneration was there endogenous light adaptation in the retina as measured by the electroretinogram. The mutant opsin was found to be invariably phosphorylated and stably bound to arrestin. Light-independent activation of transducin was demonstrated only after the removal of arrestin and dephosphorylation of K296E opsin. Thus, K296E opsin in vivo does not activate the phototransduction cascade because it is shut off by photoreceptor inactivation mechanisms. Our data show that the K296E mutation does not cause photoreceptor degeneration by continuous activation of phototransduction.