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The adhesion G-protein coupled receptor VLGR1/ADGRV1 controls autophagy
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  • Joshua Linnert,
  • Baran Güler,
  • Jacek Krzysko,
  • Uwe Wolfrum
Joshua Linnert
Johannes Gutenberg Universitat Mainz
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Baran Güler
Johannes Gutenberg Universitat Mainz
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Jacek Krzysko
Johannes Gutenberg Universitat Mainz
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Uwe Wolfrum
Johannes Gutenberg Universitat Mainz

Corresponding Author:wolfrum@uni-mainz.de

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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.
21 Dec 2022Submitted to Basic & Clinical Pharmacology & Toxicology
03 Jan 2023Submission Checks Completed
03 Jan 2023Assigned to Editor
03 Jan 2023Review(s) Completed, Editorial Evaluation Pending
03 Jan 2023Reviewer(s) Assigned
06 Feb 2023Editorial Decision: Revise Major
27 Feb 20231st Revision Received
28 Feb 2023Review(s) Completed, Editorial Evaluation Pending
28 Feb 2023Submission Checks Completed
28 Feb 2023Assigned to Editor
01 Mar 2023Reviewer(s) Assigned
22 Mar 2023Editorial Decision: Revise Minor
27 Mar 20232nd Revision Received
28 Mar 2023Review(s) Completed, Editorial Evaluation Pending
28 Mar 2023Submission Checks Completed
28 Mar 2023Assigned to Editor
28 Mar 2023Editorial Decision: Accept