Transducin Partners Outside the Phototransduction Pathway.
Transducin Partners Outside the Phototransduction Pathway.
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跨核蛋白在光转导途径之外的合作伙伴。
DOI：
10.3389/fncel.2020.589494
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发表时间：
2020
影响因子：
5.3
通讯作者：
Artemyev NO
中科院分区：
文献类型：
--
作者：
Srivastava D;Yadav RP;Inamdar SM;Huang Z;Sokolov M;Boyd K;Artemyev NO
转导蛋白在经典的G蛋白偶联受体（GPCR）光转导级联中介导信号转导。转导蛋白与受体和效应分子的相互作用已被广泛研究，目前在原子水平上定义。然而，视杆细胞转导素α（Gαt1）和βγ（Gβ1γ1）在视觉通路外的伴侣和功能尚不清楚。特别是，光诱导的杆转导蛋白从外节到内节和突触末端（IS/ST）的重新分布允许Gαt1和/或Gβ1γ1调节从杆到杆双极细胞（RBC）的突触传递。这种调制背后的蛋白质-蛋白质相互作用在很大程度上是未知的。我们讨论了杆IS/ST隔室中transducin的已知相互作用物以及导致光分散Gαt1和Gβ1γ1突触效应的潜在途径。此外，我们发现，一个突出的非GPCR鸟嘌呤核苷酸交换因子（GEF）和Gα亚基的伴侣，胆碱酯酶8A（Ric-8A）蛋白抑制剂的抗性，在整个视网膜包括感光细胞的表达。Ric-8A单独和与Gα亚基复合的最新结构已经阐明了Ric-8A活性的结构基础。为了开始定义视杆细胞感光器和视网膜中蛋白质的功能作用，我们产生了视杆细胞中Ric-8A条件性敲除的小鼠模型。我们的分析表明Ric-8A不是Gαt1的专性伴侣。Ric-8A作为GEF、运输伴侣或Gαt1突触效应的介导者的可能作用需要进一步研究。
Transducin mediates signal transduction in a classical G protein-coupled receptor (GPCR) phototransduction cascade. Interactions of transducin with the receptor and the effector molecules had been extensively investigated and are currently defined at the atomic level. However, partners and functions of rod transducin α (Gαt1) and βγ (Gβ1γ1) outside the visual pathway are not well-understood. In particular, light-induced redistribution of rod transducin from the outer segment to the inner segment and synaptic terminal (IS/ST) allows Gαt1 and/or Gβ1γ1 to modulate synaptic transmission from rods to rod bipolar cells (RBCs). Protein-protein interactions underlying this modulation are largely unknown. We discuss known interactors of transducin in the rod IS/ST compartment and potential pathways leading to the synaptic effects of light-dispersed Gαt1 and Gβ1γ1. Furthermore, we show that a prominent non-GPCR guanine nucleotide exchange factor (GEF) and a chaperone of Gα subunits, resistance to inhibitors of cholinesterase 8A (Ric-8A) protein, is expressed throughout the retina including photoreceptor cells. Recent structures of Ric-8A alone and in complexes with Gα subunits have illuminated the structural underpinnings of the Ric-8A activities. We generated a mouse model with conditional knockout of Ric-8A in rods in order to begin defining the functional roles of the protein in rod photoreceptors and the retina. Our analysis suggests that Ric-8A is not an obligate chaperone of Gαt1. Further research is needed to investigate probable roles of Ric-8A as a GEF, trafficking chaperone, or a mediator of the synaptic effects of Gαt1.
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影响因子：
4.8
作者：
Bernard, ML;Peterson, YK;Lanier, SM
通讯作者：
Lanier, SM
影响因子：
33.6
作者：
Do MT;Yau KW
通讯作者：
Yau KW
DOI：
10.4049/jimmunol.1500523
发表时间：
2015-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boularan C;Hwang IY;Kamenyeva O;Park C;Harrison K;Huang Z;Kehrl JH
通讯作者：
Kehrl JH
影响因子：
5.3
作者：
Dhingra, A;Jiang, MS;Vardi, N
通讯作者：
Vardi, N
影响因子：
16
作者：
Gao, Yang;Hu, Hongli;Skiniotis, Georgios
通讯作者：
Skiniotis, Georgios