当前位置: X-MOL 学术Cell. Mol. Life Sci. › 论文详情
GPR50-Ctail cleavage and nuclear translocation: a new signal transduction mode for G protein-coupled receptors.
Cellular and Molecular Life Sciences ( IF 7.014 ) Pub Date : 2020-01-03 , DOI: 10.1007/s00018-019-03440-7
Raise Ahmad,Olivier Lahuna,Anissa Sidibe,Avais Daulat,Qiang Zhang,Marine Luka,Jean-Luc Guillaume,Sarah Gallet,François Guillonneau,Juliette Hamroune,Sophie Polo,Vincent Prévot,Philippe Delagrange,Julie Dam,Ralf Jockers

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.
更新日期:2020-01-04

 

全部期刊列表>>
宅家赢大奖
向世界展示您的会议墙报和演示文稿
全球疫情及响应:BMC Medicine专题征稿
新版X-MOL期刊搜索和高级搜索功能介绍
化学材料学全球高引用
ACS材料视界
x-mol收录
自然科研论文编辑服务
南方科技大学
南方科技大学
舒伟
中国科学院长春应化所于聪-4-8
复旦大学
课题组网站
X-MOL
香港大学化学系刘俊治
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug