Structural features and disease-associated functions of ADGRV1: insights from signaling mechanisms.
8 affiliations
- 1Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. [email protected].
- 2Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
- 3Department of Stomatology, Xi'an Honghui Hospital Yanliang Branch, Xi'an, China.
- 4Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
- 5Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. [email protected].
- 6Department of Scientific Research, Medical Affairs Office, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. [email protected].
- 7College of Animal Science and Technology, Northwest A&F University, Yangling, China. [email protected].
- 8Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. [email protected].
Abstract
Adhesion G protein-coupled receptor V1 (ADGRV1) is one of the largest and most modular receptors in the adhesion G protein-coupled receptor (aGPCR) family, integrating functions of cell adhesion, mechanosensing, and classical G protein signaling. Its structural domains, including calcium exchanger β (Calx-β) repeats, laminin G-like/ pentraxin (LamG/PTX) domain, epilepsy-associated (EPTP/EAR) repeats, GPCR-autoproteolysis-inducing (GAIN) domain/GPCR proteolytic site (GPS) module with tethered Stachel peptide, seven transmembrane (7TM) helices, and PDZ-binding motif (PBM), jointly shape its activation, intracellular transport, and effector coupling. Recent studies indicate that ADGRV1 exhibits context-dependent signaling, particularly through G protein coupling and ciliary localization, thereby influencing calcium homeostasis, autophagy, and developmental pathways. Genetic and functional evidence links ADGRV1 to Usher syndrome (USH) type II, epilepsy, and emerging associations with Alzheimer's disease (AD), and recurrent somatic alterations in diverse cancers. Variants in ADGRV1 modulate processes such as ankle-link complex (ALC) assembly, synaptic stability, amyloid and tau regulation, chemoresistance, and immune microenvironment remodeling. Despite this progress, many aspects of its signaling mechanisms, ligand interactions, and disease relevance remain poorly understood. Future work combining high-resolution structural studies, systematic mapping of signaling bias, and rigorous translational validation will be essential to clarify the multifaceted roles of ADGRV1 and to evaluate its potential as a biomarker and therapeutic target.
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BibTeX
@article{liu2026structural,
title = {{Structural features and disease-associated functions of ADGRV1: insights from signaling mechanisms.}},
author = {Qiao Liu and Jing Tian and Lu Xin and Fei Liu and Hong-Ying Jiao and Xiao-Lan Li and Lan-Lan Feng and Wei Zhang and Zeng-Hui Fan and Yang Li and Li Gong},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = aug,
doi = {10.1186/s12964-026-03149-8},
url = {https://europepmc.org/article/MED/42972392},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Structural features and disease-associated functions of ADGRV1: insights from signaling mechanisms.
AU - Qiao Liu
AU - Jing Tian
AU - Lu Xin
AU - Fei Liu
AU - Hong-Ying Jiao
AU - Xiao-Lan Li
AU - Lan-Lan Feng
AU - Wei Zhang
AU - Zeng-Hui Fan
AU - Yang Li
AU - Li Gong
PY - 2026
DA - 2026/08/12
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03149-8
UR - https://europepmc.org/article/MED/42972392
AB - Adhesion G protein-coupled receptor V1 (ADGRV1) is one of the largest and most modular receptors in the adhesion G protein-coupled receptor (aGPCR) family, integrating functions of cell adhesion, mechanosensing, and classical G protein signaling. Its structural domains, including calcium exchanger β (Calx-β) repeats, laminin G-like/ pentraxin (LamG/PTX) domain, epilepsy-associated (EPTP/EAR) repeats, GPCR-autoproteolysis-inducing (GAIN) domain/GPCR proteolytic site (GPS) module with tethered Stachel peptide, seven transmembrane (7TM) helices, and PDZ-binding motif (PBM), jointly shape its activation, intracellular transport, and effector coupling. Recent studies indicate that ADGRV1 exhibits context-dependent signaling, particularly through G protein coupling and ciliary localization, thereby influencing calcium homeostasis, autophagy, and developmental pathways. Genetic and functional evidence links ADGRV1 to Usher syndrome (USH) type II, epilepsy, and emerging associations with Alzheimer's disease (AD), and recurrent somatic alterations in diverse cancers. Variants in ADGRV1 modulate processes such as ankle-link complex (ALC) assembly, synaptic stability, amyloid and tau regulation, chemoresistance, and immune microenvironment remodeling. Despite this progress, many aspects of its signaling mechanisms, ligand interactions, and disease relevance remain poorly understood. Future work combining high-resolution structural studies, systematic mapping of signaling bias, and rigorous translational validation will be essential to clarify the multifaceted roles of ADGRV1 and to evaluate its potential as a biomarker and therapeutic target.
SN - 1478-811X
ER -