• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Effect of the ILE86TER mutation in the γ subunit of cGMP phosphodiesterase (PDE6) on rod photoreceptor signaling
【24h】

Effect of the ILE86TER mutation in the γ subunit of cGMP phosphodiesterase (PDE6) on rod photoreceptor signaling

机译：cGMP磷酸二酯酶（PDE6）γ亚基中ILE86TER突变对棒状光感受器信号传导的影响

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The light-dependent decrease in cyclic guanosine monophosphate (cGMP) in the rod outer segment is produced by a phosphodiesterase (PDE6), consisting of catalytic α and β subunits and two inhibitory γ subunits. The molecular mechanism of PDE6γ regulation of the catalytic subunits is uncertain. To study this mechanism in vivo, we introduced a modified Pde6g gene for PDE6γ into a line of Pde6g ~(tm1)/Pde6g ~(tm1) mice that do not express PDE6γ. The resulting ILE86TER mice have a PDE6γ that lacks the two final carboxyl-terminal Ile ~(86) and Ile ~(87) residues, a mutation previously shown in vitro to reduce inhibition by PDE6γ. ILE86TER rods showed a decreased sensitivity and rate of activation, probably the result of a decreased level of expression of PDE6 in ILE86TER rods. More importantly, they showed a decreased rate of decay of the photoresponse, consistent with decreased inhibition of PDE6 α and β by PDE6γ. Furthermore, ILE86TER rods had a higher rate of spontaneous activation of PDE6 than WT rods. Circulating current in ILE86TER rods that also lacked both guanylyl cyclase activating proteins (GCAPs) could be increased several fold by perfusion with 100μM of the PDE6 inhibitor 3-isobutyl-1-methylxanthine (IBMX), consistent with a higher rate of dark PDE6 activity in the mutant photoreceptors. In contrast, IBMX had little effect on the circulating current of WT rods, unlike previous results from amphibians. Our results show for the first time that the Ile ~(86) and Ile ~(87) residues are necessary for normal inhibition of PDE6 catalytic activity in vivo, and that increased basal activity of PDE can be partially compensated by GCAP-dependent regulation of guanylyl cyclase.
机译：杆外部的环状鸟苷单磷酸酯（cGMP）的光依赖性降低是由磷酸二酯酶（PDE6）引起的，磷酸二酯酶由催化的α和β亚基和两个抑制性γ亚基组成。催化亚基的PDE6γ调控的分子机理尚不确定。为了在体内研究该机制，我们将修饰的PDE6γPde6g基因引入了不表达PDE6γ的Pde6g〜（tm1）/ Pde6g〜（tm1）小鼠品系中。所得的ILE86TER小鼠的PDE6γ缺少两个最终的羧基末端Ile〜（86）和Ile〜（87）残基，该突变先前已在体外显示出可减少PDE6γ的抑制作用。 ILE86TER棒显示出降低的敏感性和活化速率，这可能是ILE86TER棒中PDE6表达水平降低的结果。更重要的是，它们显示出光响应的衰减速率降低，这与PDE6γ对PDE6α和β的抑制作用降低有关。此外，ILE86TER棒比野生型棒具有更高的PDE6自发活化率。通过同时灌注100μMPDE6抑制剂3-异丁基-1-甲基黄嘌呤（IBMX），ILE86TER杆中也缺少鸟苷酸环化酶激活蛋白（GCAP）的循环电流可以增加数倍，这与较高的深色PDE6活性相一致。突变体感光器。相反，IBMX对WT棒的循环电流影响很小，这与两栖动物先前的结果不同。我们的结果首次表明，Ile〜（86）和Ile〜（87）残基对于体内正常抑制PDE6催化活性是必需的，并且PDE基础活性的提高可以通过GCAP依赖性GCAP调节来部分补偿。鸟苷酸环化酶。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号