Implications of dimeric activation of PDE6 for rod phototransduction.
Implications of dimeric activation of PDE6 for rod phototransduction.
复制标题
PDE6 二聚体激活对杆光转导的影响。
DOI：
10.1098/rsob.180076
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发表时间：
2018
期刊：
影响因子：
5.8
通讯作者：
Kraft,TimothyW
中科院分区：
文献类型：
--
作者：
Lamb,TrevorD;Heck,Martin;Kraft,TimothyW
我们研究的影响，最近的一份报告提供的证据表明，两个转导必须结合到杆磷酸二酯酶引起显着的水解活性。为了预测视杆光感受器的电响应，我们使用的相互作用的分子在光盘膜的表面的二维扩散接触的数值模拟，然后我们使用模拟的PDE活性作为下游反应级联的驱动函数。这些结果解释了以前一直令人困惑的视杆细胞光转导的许多方面。例如，他们解释了杆细胞比锥细胞存在更大的初始延迟。此外，我们的分析表明，在黑暗中记录在杆的“连续”噪音可能会出现自发激活的个别分子的PDE在一个速率为几十每秒每杆，可能是由于自发激活的transducins在一个速率为数千每秒每杆。因此，杆中PDE的二聚体活化提供了针对自发转导蛋白活化的免疫力，从而降低了连续噪声。我们的分析还提供了一个连贯的定量解释的放大单光子响应。总体而言，PDE的二聚体活化的数值分析将杆光转导置于新的光中。
We examine the implications of a recent report providing evidence that two transducins must bind to the rod phosphodiesterase to elicit significant hydrolytic activity. To predict the rod photoreceptor's electrical response, we use numerical simulation of the two-dimensional diffusional contact of interacting molecules at the surface of the disc membrane, and then we use the simulated PDE activity as the driving function for the downstream reaction cascade. The results account for a number of aspects of rod phototransduction that have previously been puzzling. For example, they explain the existence of a greater initial delay in rods than in cones. Furthermore, our analysis suggests that the ‘continuous’ noise recorded in rods in darkness is likely to arise from spontaneous activation of individual molecules of PDE at a rate of a few tens per second per rod, probably as a consequence of spontaneous activation of transducins at a rate of thousands per second per rod. Hence, the dimeric activation of PDE in rods provides immunity against spontaneous transducin activation, thereby reducing the continuous noise. Our analysis also provides a coherent quantitative explanation of the amplification underlying the single photon response. Overall, numerical analysis of the dimeric activation of PDE places rod phototransduction in a new light.