From the Department of Pharmacology and the Center for Molecular Neuroscience and the Vision Research Center, Vanderbilt University, Nashville, Tennessee 37232
From the Department of Pharmacology and the Center for Molecular Neuroscience and the Vision Research Center, Vanderbilt University, Nashville, Tennessee 37232.
J Biol Chem. 2014 Jun 27;289(26):18526-34. doi: 10.1074/jbc.M114.571224. Epub 2014 May 16.
Arrestin regulates many facets of G-protein coupled receptor signaling. In Drosophila, Arrestin 1 (Arr1) is expressed at a lower level than Arrestin 2 (Arr2), and the role of Arr1 in visual physiology is less understood. Here we generated transgenic flies expressing enhanced green fluorescent protein tagged Arr1 (Arr1-eGFP) and explored its trafficking in live photoreceptors. We show that Arr1-eGFP is localized in the cytoplasm and displays light-dependent translocation to the rhabdomere possibly by interacting with photoactivated rhodopsin 1 (Rh1*). In the adult, translocation of Arr1-eGFP occurs with slower kinetics when compared with that of Arr2-eGFP. This slower kinetic activity may be attributable to a reduced level of phosphorylated Rh1*. Indeed, a reduced level of phosphorylated Rh1* recruits a lower level of Arr1-eGFP to rhabdomeres. To investigate whether Arr1 is required for the deactivation of phosphorylated Rh1*, we show that in flies with reduced Arr1 prolonged depolarizing afterpotential can be triggered with fewer light pulses, indicating that inactivation of phosphorylated Rh1* is compromised when the Arr1 level is reduced. Consistently, Arr1 is no longer required for deactivation of Rh1 in flies expressing phosphorylation-deficient Rh1. Previously it was reported that Arr1 displays light-dependent internalization. Unexpectedly, in adult photoreceptors we failed to observe endocytosis of Arr1-eGFP. In contrast, we show that in pupal photoreceptors Arr1-eGFP becomes internalized and sequestered in vesicles within the cytoplasm. Taken together, we propose that Arr1 plays distinct roles during development and adulthood. Arr1 orchestrates the recycling of phosphorylated Rh1* in pupae whereas it regulates the deactivation in adult.
抑制蛋白调节 G 蛋白偶联受体信号的多个方面。在果蝇中,抑制蛋白 1(Arr1)的表达水平低于抑制蛋白 2(Arr2),其在视觉生理学中的作用知之甚少。在这里,我们生成了表达增强型绿色荧光蛋白标记的 Arr1(Arr1-eGFP)的转基因果蝇,并探索了其在活感光细胞中的运输。我们表明 Arr1-eGFP 定位于细胞质中,并通过与光激活的视紫红质 1(Rh1*)相互作用显示出对光的依赖性易位到光感受器纤毛。在成年期,与 Arr2-eGFP 相比,Arr1-eGFP 的易位动力学较慢。这种较慢的动力学活性可能归因于磷酸化 Rh1的水平降低。事实上,磷酸化 Rh1的水平降低会募集较少的 Arr1-eGFP 到光感受器纤毛。为了研究 Arr1 是否需要磷酸化 Rh1的失活,我们表明在 Arr1 水平降低的果蝇中,用较少的光脉冲可以触发延长的去极化后电位,这表明磷酸化 Rh1的失活受到损害。一致地,当 Arr1 水平降低时,Arr1 不再需要用于失活表达磷酸化缺陷型 Rh1 的果蝇中的 Rh1。以前有报道称 Arr1 显示出对光的依赖性内化。出乎意料的是,在成年感光细胞中,我们未能观察到 Arr1-eGFP 的内吞作用。相比之下,我们表明在蛹感光细胞中,Arr1-eGFP 被内化并在细胞质中的囊泡中隔离。总之,我们提出 Arr1 在发育和成年期发挥不同的作用。Arr1 在蛹中协调磷酸化 Rh1*的回收,而在成年期调节失活。