Metallophosphoesterase regulates light-induced rhodopsin endocytosis by promoting an association between arrestin and the adaptor protein AP2
Metallophosphoesterase regulates light-induced rhodopsin endocytosis by promoting an association between arrestin and the adaptor protein AP2
复制标题
金属磷酸酯酶通过促进抑制蛋白和接头蛋白 AP2 之间的关联来调节光诱导的视紫红质内吞作用
DOI：
10.1074/jbc.ra119.009602
复制
发表时间：
2019-07
影响因子：
4.8
通讯作者：
Han Junhai
中科院分区：
文献类型：
--
作者：
Mu Yawen;Tian Yao;Zhang Zi Chao;Han Junhai
视网膜中视紫红质的光诱导内吞作用对于防止光感受器过度活跃和光感受器细胞的存活至关重要。在果蝇中，这一过程由arrestin 1（Arr 1）介导。由于Arr1缺乏受体内化所需的网格蛋白结合结构域和与网格蛋白衔接蛋白AP 2的β亚基相互作用的C末端序列，Arr1如何介导主要视紫红质Rh1的内吞作用的机制尚不清楚。在这里，使用几种方法，包括Arr结合和下拉测定，免疫荧光技术，和EM成像，我们发现，果蝇金属磷酸酯酶（dMPPE）参与光诱导的视紫红质内吞作用。我们观察到，dMPPE突变体的感光细胞表现出受损的光诱导的视紫红质内吞作用，这种损害是独立的dMPPE磷酸酯酶活性。此外，dMPPE直接与Arr 1相互作用，并促进Arr 1与AP 2的关联。值得注意的是，遗传dmppe缺失通过抑制Rh1内吞作用在很大程度上防止了norpA（编码磷脂酶C）突变体中的视网膜变性，所述突变体先前被报道为促成视网膜变性。我们的研究结果表明，Arr1与AP2相互作用，dMPPE作为一个重要的调节器Rh1内吞作用和视网膜变性的功能。
Light-induced endocytosis of rhodopsin in the retina is critical for preventing photoreceptor hyperactivity and for the survival of photoreceptor cells. In Drosophila, this process is mediated by arrestin1 (Arr1). Because Arr1 lacks a clathrin-binding domain required for receptor internalization and the C-terminal sequence that interacts with the β-subunit of the clathrin adaptor protein AP2, the mechanism of how Arr1 mediates endocytosis of the major rhodopsin Rh1 is unclear. Here, using several approaches, including Arr binding and pulldown assays, immunofluorescence techniques, and EM imaging, we found that Drosophila metallophosphoesterase (dMPPE) is involved in light-induced rhodopsin endocytosis. We observed that the photoreceptor cells of a dmppe mutant exhibit impaired light-induced rhodopsin endocytosis and that this impairment is independent of dMPPE phosphoesterase activity. Furthermore, dMPPE directly interacted with Arr1 and promoted the association of Arr1 with AP2. Of note, genetic dmppe deletion largely prevented retinal degeneration in norpA (encoding phospholipase C) mutants, which were reported previously to contribute to retinal degeneration, by suppressing Rh1 endocytosis. Our findings demonstrate that Arr1 interacts with AP2 and that dMPPE functions as a critical regulator in Rh1 endocytosis and retinal degeneration.
登录
查看更多内容
影响因子：
5.5
作者：
Xiao Wang;Yawen Mu;Mengshi Sun;Junhai Han
通讯作者：
Xiao Wang;Yawen Mu;Mengshi Sun;Junhai Han
影响因子：
9.8
作者：
Hu W;Wang T;Wang X;Han J
通讯作者：
Han J
影响因子：
4.8
作者：
Rajagopal S;Shenoy SK
通讯作者：
Shenoy SK
影响因子：
7.8
作者：
Wang, Tao;Jiao, Yuchen;Montell, Craig
通讯作者：
Montell, Craig
影响因子：
16.2
作者：
Kiselev, A;Socolich, M;Ranganathan, R
通讯作者：
Ranganathan, R