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Authors: Linnert, Joshua
Güler, Baran E.
Krzysko, Jacek
Wolfrum, Uwe
Title: The adhesion G protein-coupled receptor VLGR1/ADGRV1 controls autophagy
Online publication date: 26-Jun-2023
Year of first publication: 2023
Language: english
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 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.
DDC: 570 Biowissenschaften
570 Life sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 10 Biologie
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY-NC
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Journal: Basic & clinical pharmacology & toxicology
Version of Record (VoR)
Publisher: Wiley-Blackwell
Publisher place: Oxford
Issue date: 2023
ISSN: 1742-7835
Publisher DOI: 10.1111/bcpt.13869
Appears in collections:DFG-491381577-H

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