当前位置: X-MOL 学术Cell. Mol. Life Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
GPR50-Ctail cleavage and nuclear translocation: a new signal transduction mode for G protein-coupled receptors.
Cellular and Molecular Life Sciences ( IF 8 ) Pub Date : 2020-01-03 , DOI: 10.1007/s00018-019-03440-7
Raise Ahmad 1 , Olivier Lahuna 1 , Anissa Sidibe 1 , Avais Daulat 1 , Qiang Zhang 1 , Marine Luka 1 , Jean-Luc Guillaume 1 , Sarah Gallet 2 , François Guillonneau 1 , Juliette Hamroune 1 , Sophie Polo 3 , Vincent Prévot 2 , Philippe Delagrange 4 , Julie Dam 1 , Ralf Jockers 1
Affiliation  

Transmission of extracellular signals by G protein-coupled receptors typically relies on a cascade of intracellular events initiated by the activation of heterotrimeric G proteins or β-arrestins followed by effector activation/inhibition. Here, we report an alternative signal transduction mode used by the orphan GPR50 that relies on the nuclear translocation of its carboxyl-terminal domain (CTD). Activation of the calcium-dependent calpain protease cleaves off the CTD from the transmembrane-bound GPR50 core domain between Phe-408 and Ser-409 as determined by MALDI-TOF-mass spectrometry. The cytosolic CTD then translocates into the nucleus assisted by its ‘DPD’ motif, where it interacts with the general transcription factor TFII-I to regulate c-fos gene transcription. RNA-Seq analysis indicates a broad role of the CTD in modulating gene transcription with ~ 8000 differentially expressed genes. Our study describes a non-canonical, direct signaling mode of GPCRs to the nucleus with similarities to other receptor families such as the NOTCH receptor



中文翻译:

GPR50-尾裂和核易位:G蛋白偶联受体的新信号转导模式。

G蛋白偶联受体的细胞外信号的传递通常依赖于细胞内事件的级联,该事件由异源三聚体G蛋白或β-arrestin的激活以及效应子的激活/抑制引发。在这里,我们报告孤儿GPR50使用的一种替代信号转导模式,该模式依赖于其羧基末端结构域(CTD)的核易位。钙依赖性钙蛋白酶蛋白酶的激活从MALDI-TOF-质谱法测定的Phe-408和Ser-409之间跨膜结合的GPR50核心结构域中切断了CTD。然后,胞质CTD在其“ DPD”基序的辅助下易位到核中,在其中与通用转录因子TFII-1相互作用,调节c-fos基因的转录。RNA-Seq分析表明CTD在调节约8000个差异表达基因的基因转录中具有广泛的作用。我们的研究描述了GPCR向细胞核的非规范,直接信号转导模式,与其他受体家族(如NOTCH受体)相似

更新日期:2020-01-03
down
wechat
bug