《分子細(xì)胞生物學(xué)》（Molecular and Cellular Biology）近日發(fā)表了中科院上海生命科學(xué)研究院營養(yǎng)所營養(yǎng)與代謝重點(diǎn)實(shí)驗(yàn)室陳雁研究組博士生蔣玉輝等對(duì)于RKTG調(diào)控Gβγ功能的最新研究結(jié)果,。
G蛋白偶聯(lián)受體（GPCR）參與了機(jī)體內(nèi)多種生理過程的調(diào)節(jié)，是目前治療多種人類疾病包括代謝性疾病的藥物靶點(diǎn),。GPCR的G蛋白部分由Gα,，β，γ三個(gè)亞基組成,，受體激活后,，其信號(hào)轉(zhuǎn)導(dǎo)主要由α亞基進(jìn)行,。但近年來的研究表明,，Gβγ可以不依賴Gα發(fā)揮許多重要的生理功能,，如調(diào)節(jié)離子通道、磷脂酰肌醇激酶以及G蛋白偶聯(lián)受體激酶（GRK）等重要的細(xì)胞內(nèi)分子,。
RKTG是一個(gè)特異表達(dá)在細(xì)胞器高爾基體的一個(gè)膜蛋白,。研究人員首先發(fā)現(xiàn)RKTG與Gβγ相互作用，在空間上把細(xì)胞內(nèi)的Gβγ轉(zhuǎn)移到高爾基體,，發(fā)現(xiàn)RKTG通過改變Gβγ空間位置對(duì)細(xì)胞生理功能帶來影響,。RKTG能夠與GRK競爭性結(jié)合Gβγ,，影響了GRK介導(dǎo)的G蛋白偶聯(lián)受體內(nèi)吞，進(jìn)而影響了G蛋白信號(hào)通路的脫敏效應(yīng),。RKTG 通過與Gβγ結(jié)合,，影響了Gβγ下游的PI3K/AKT信號(hào)通路。RKTG與Gβγ結(jié)合時(shí)間曲線與AKT活化時(shí)間曲線呈負(fù)相關(guān),，而RKTG的缺失，減少了GPCR激活后Gβγ在高爾基體的分布以及AKT的活化,。
該項(xiàng)研究發(fā)現(xiàn)了調(diào)控Gβγ功能的一個(gè)全新機(jī)制,，對(duì)于深入了解G蛋白信號(hào)通路有著重要的意義。另外,，由于Gβγ下游效應(yīng)分子參與了多個(gè)細(xì)胞功能的調(diào)節(jié),，該研究為未來醫(yī)學(xué)領(lǐng)域中一些疾病的治療增添了新的理論基礎(chǔ)以及藥物靶點(diǎn)。
該研究受到科技部重大科學(xué)研究計(jì)劃,，國家基金委重點(diǎn)項(xiàng)目,、杰出青年基金，中科院重大項(xiàng)目等基金的支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Mol. Cell. Biol. doi:10.1128/MCB.01038-09
Regulation of G protein signaling by RKTG via sequestrating Gbetagamma subunit to Golgi apparatus
Yuhui Jiang, Xiaoduo Xie, Yixuan Zhang, Xiaolin Luo, Xiao Wang, Fengjuan Fan, Dawei Zheng, Zhenzhen Wang, and Yan Chen*
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Upon ligand binding, G protein coupled receptors (GPCRs) impart the signal to heterotrimeric G proteins composed of , and subunits, leading to dissociation of G subunit from G subunit. While the G subunit is imperative for downstream signaling, the G subunit, in its own right, mediates a variety of cellular responses such as GPCR desensitization via recruiting GRK to plasma membrane and AKT stimulation. Here we report a mode of spatial regulation of G subunit through alteration in subcellular compartmentation. RKTG (Raf Kinase Trapping to Golgi) is a newly characterized membrane protein specifically localized at the Golgi apparatus. The N-terminus of RKTG interacts with Gand tethers G to the Golgi. Overexpression of RKTG impedes the interaction of G with GRK2, abrogates the ligand-induced change of subcellular distribution of GRK2, reduces isoproterenol-stimulated phosphorylation of 2-adrenergic receptor (2AR), and alters 2AR desensitization. In addition, RKTG inhibits G- and ligand-mediated AKT that is enhanced in cells with downregulation of RKTG. Silencing of RKTG also enhances GRK2 internalization and compromises ligand-induced G translocation to the Golgi apparatus. Taken together, our results reveal that RKTG can modulate GPCR signaling through sequestering G to the Golgi apparatus and whereby attenuating the functions of G.
