11-cis-retinal reduces constitutive opsin phosphorylation and improves quantum catch in retinoid-deficient mouse rod photoreceptors
11-cis-retinal reduces constitutive opsin phosphorylation and improves quantum catch in retinoid-deficient mouse rod photoreceptors
复制标题
DOI：
10.1074/jbc.m205507200
复制
发表时间：
2002-10-25
影响因子：
4.8
通讯作者：
Rohrer, B
中科院分区：
文献类型：
--
作者：
Ablonczy, Z;Crouch, RK;Rohrer, B
Rpe 65（-/-）小鼠产生最少量的11-顺式-视黄醛，这是形成光敏视色素所必需的配体。因此，这些动物的脱辅基蛋白视蛋白没有暴露于其正常配体。Rpe 65（-/-）小鼠含有小于0.1%的野生型水平的视紫红质。Rpe 65（-/-）小鼠的视蛋白质谱分析显示，在暗适应小鼠中磷酸化水平异常高，但没有其他结构改变。1月龄动物的单闪光和闪烁视网膜电图（ERG）显示了微量视杆细胞功能，但没有视锥细胞反应。单闪光ERG的B波动力学与含有完全互补的视紫红质的暗适应野生型小鼠的B波动力学相当。对Rpe 65（-/-）小鼠应用（腹膜内注射）11-顺式-视黄醛可增加视杆ERG信号，增加视紫红质水平，并降低视蛋白磷酸化。因此，外源性11-顺式-视黄醛通过再生视紫红质和去除组成性视蛋白磷酸化来改善光感受器功能。我们的研究结果表明，视蛋白，这还没有暴露于11-顺式-视网膜，不产生的活动通常与漂白脱辅基蛋白。
Rpe65(-/-) mice produce minimal amounts of 11-cis-retinal, the ligand necessary for the formation of photosensitive visual pigments. Therefore, the apoprotein opsin in these animals has not been exposed to its normal ligand. The Rpe65(-/-) mice contain less than 0.1% of wild type levels of rhodopsin. Mass spectrometric analysis of opsin from Rpe65(-/-) mice revealed unusually high levels of phosphorylation in dark-adapted mice but no other structural alterations. Single flash and flicker electroretinograms (ERGs) from 1-month-old animals showed trace rod function but no cone response. B-wave kinetics of the single-flash ERG are comparable with those of dark-adapted wild type mice containing a full compliment of rhodopsin. Application (intraperitoneal injection) of 11-cis-retinal to Rpe65(-/-) mice increased the rod ERG signal, increased levels of rhodopsin, and decreased opsin phosphorylation. Therefore, exogenous 11-cis-retinal improves photoreceptor function by regenerating rhodopsin and removes constitutive opsin phosphorylation. Our results indicate that opsin, which has not been exposed to 11-cis-retinal, does not generate the activity generally associated with the bleached apoprotein.