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Updated: Sep 22, 2025

Detection of Ligand-activated G Protein-coupled Receptor Internalization by Confocal Microscopy
Published on: April 9, 2017
Posttranslational modifications in GPCR internalization
Xueqing Tang1,2,3, Jingwei Bian1,2,3, Zijian Li1,2,3,4
1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, People's Republic of China.
Abstract:
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors that serve as the most important drug targets. Classically, GPCR internalization has been considered to lead to receptor desensitization. However, many studies over the past decade have reported that internalized membrane receptors can trigger distinct signal activation. The "internalized activation" provides a completely new understanding for the receptor internalization, the mechanism of physiology/pathology and novel drug targets for precision medicine. GPCR internalization undergoes a series of strict regulations, especially by posttranslational modifications (PTMs). Here, this review summarizes different PTMs in GPCR internalization and analyzes their significance in GPCR internalization dynamics, internalization routes, postinternalization fates, and related diseases, which will offer new insights into the regulatory mechanism of GPCR signaling and novel drug targets for precision medicine.
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