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Insulin receptor regulates photoreceptor CNG channel activity

机译:胰岛素受体调节感光器CNG通道活性

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Photoreceptor cyclic nucleotide gated (CNG) channels are critical elements in phototransduction and light adaptation. Here we report that insulin receptor (IR), an integral membrane protein, directly phosphorylates the CNGA1 subunit of CNG channels that in turn affects the function of these channels negatively. The IR phosphorylates Tyr498 and Tyr503 residues on CNGA1 that are situated at the membrane-cytoplasmic interface. The IR tyrosine kinase activity is essential for the inhibition of CNG channel. To maintain the channels in an off state, it is necessary not only to have a precise balance of the cGMP levels but also to have a control on the cGMP sensitivity of the CNG channels itself. In this study, we observed that the channel opens at a lower concentration of cGMP in IR~(-/-) mice. These studies suggest that IR regulates the modulation of CNG channel activity in vivo.
机译:光感受器环状核苷酸门控(CNG)通道是光转导和光适应中的关键要素。在这里,我们报告胰岛素受体(IR),一种完整的膜蛋白,直接磷酸化CNG通道的CNGA1亚基,进而对这些通道的功能产生负面影响。 IR磷酸化CNGA1上位于膜-细胞质界面的Tyr498和Tyr503残基。 IR酪氨酸激酶活性对于抑制CNG通道至关重要。为了将通道保持在关闭状态,不仅需要精确地平衡cGMP水平,还需要控制CNG通道本身的cGMP敏感性。在这项研究中,我们观察到该通道在IR〜(-/-)小鼠中以较低的cGMP浓度打开。这些研究表明,IR调节体内CNG通道活性的调节。

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