Arrestin competition influences the kinetics and variability of the single-photon responses of mammalian rod photoreceptors.
Arrestin competition influences the kinetics and variability of the single-photon responses of mammalian rod photoreceptors.
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DOI：
10.1523/jneurosci.0819-09.2009
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发表时间：
2009-09-23
期刊：
影响因子：
--
通讯作者：
Rieke F
中科院分区：
文献类型：
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作者：
Doan T;Azevedo AW;Hurley JB;Rieke F
通过g蛋白偶联受体的可靠信号转导需要适当的受体失活。例如，来自单个视紫红质分子的信号在不同分子之间变化很小，这就需要通过磷酸化和抑制蛋白结合来实现视紫红质的可重复性失活。我们确定了视紫红质激酶（GRK1）和/或arrestin1浓度的降低如何影响小鼠杆状细胞单光子反应的动力学和变异性。这些实验表明，抑制蛋白除了在猝灭视紫红质活性中起作用外，还可以通过与GRK1竞争来调节视紫红质磷酸化的动力学。这种竞争影响了视紫红质活性寿命的变异性。偏向GRK1的竞争表明，在我们的实验条件下，视紫红质在大部分单光子响应中保持活跃。这种持久的视紫红质活性可以解释单光子响应变异性的特征时间过程。事实上，解释方差的晚峰时间需要视紫红质活性寿命大约是g蛋白转导蛋白活性寿命的两倍。抑制因子和激酶之间的竞争可能是影响g蛋白偶联受体介导的信号的一般手段，特别是当少数受体的激活产生具有重要功能的信号时。
Reliable signal transduction via G-protein coupled receptors requires proper receptor inactivation. For example, signals originating from single rhodopsin molecules vary little from one to the next, requiring reproducible inactivation of rhodopsin by phosphorylation and arrestin binding. We determined how reduced concentrations of rhodopsin kinase (GRK1) and/or arrestin1 influenced the kinetics and variability of the single-photon responses of mouse rods. These experiments revealed that arrestin, in addition to its role in quenching rhodopsin's activity, can tune the kinetics of rhodopsin phosphorylation by competing with GRK1. This competition influenced the variability of rhodopsin's active lifetime. Biasing the competition in favor of GRK1 revealed that rhodopsin remained active through much of the single-photon response under the conditions of our experiments. This long-lasting rhodopsin activity can explain the characteristic time course of single-photon response variability. Indeed, explaining the late time-to-peak of the variance required an active lifetime of rhodopsin about twice that of the G-protein transducin. Competition between arrestins and kinases may be a general means of influencing signals mediated by G-protein coupled receptors, particularly when activation of a few receptors produces signals of functional importance.