The adhesion G-protein coupled receptor VLGR1/ADGRV1 controls autophagy

Abstract

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest known adhesion G protein-coupled receptor. Mutations in VLGR1/ADGRV1 cause Usher syndrome (USH), the most common form of hereditary deaf-blindness, and have been additionally linked to epilepsy. Although VLGR1/ADGRV1 is almost ubiquitously expressed, little is known about the subcellular function and signalling of the VLGR1 protein and thus about mechanisms underlying the development of diseases. Using affinity proteomics, we have identified key components of autophagosomes as putative interacting proteins of VLGR1. In addition, whole transcriptome sequencing of the retinae of the Vlgr1/del7TM mouse model revealed altered expression profiles of gene-related autophagy. Monitoring autophagy by immunoblotting and immunocytochemistry of the LC3 and p62 as autophagy marker proteins revealed evoked autophagy in VLGR1-deficient hTERT-RPE1 cells and USH2C patient-derived fibroblasts. Our data demonstrate the molecular and functional interaction of VLGR1 with key components of the autophagy process and point to an essential role of VLGR1 in the regulation of autophagy at internal membranes. The close association of VLGR1 with autophagy helps to explain the pathomechanisms underlying human USH and epilepsy-related to VLGR1 defects.

Adhesion G protein‐coupled receptor's structure, function and role in biology—Status from the 10th adhesion GPCR workshop in Copenhagen, 2022

“…From a different perspective, Linnert et al (Wolfrum group) 26 investigate the subcellular function and signalling of ADGRV1 and establish a role in autophagy, an intracellular degradation process for cytoplasmic contents. Using affinity proteomics, the authors identify key components of autophagy as putative interacting proteins of VLGR1.…”

Welcome to Basic & Clinical Pharmacology & Toxicology 2024

“…As we embark on the new year, we invite you to explore the wealth of knowledge and exciting content our journal offers. In 2023, we published three Special Collections from focused conferences supported by the Nordic Association for the Publication of Basic and Clinical Pharmacology and Toxicology, including Adhesion G‐Protein‐coupled Receptors, 1–10 Transmembrane Transporter Proteins: Catching Transport in Motion 11–19 and Advancing Deprescribing: Learnings from the first International Conference on Deprescribing 20–31 . The second part of the latter Special Collection will appear in the January 2024 issue.…”