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The adhesion GPCR VLGR1/ADGRV1 regulates focal adhesion turnover by controlling their assembly
  • Baran Güler,
  • Joshua Linnert,
  • Uwe Wolfrum
Baran Güler
Johannes Gutenberg Universitat Mainz
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Joshua Linnert
Johannes Gutenberg Universitat Mainz
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Uwe Wolfrum
Johannes Gutenberg Universitat Mainz

Corresponding Author:[email protected]

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Abstract

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhesion G protein-coupled receptor aGPCRs. Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome (USH), the most common form of deaf-blindness, and also with epilepsy in humans and in mice. Although VLGR1 is almost ubiquitously expressed in CNS and ocular and inner ear sensory cells. Little is known about the pathogenesis of the diseases related to VLGR1. We previously identified VLGR1 as a vital component of focal adhesions (FA) serving as a metabotropic mechanoreceptor that controls cell spreading and migration. FAs are highly dynamic and turnover frequently in response to internal and external signals. Here, we aimed to elucidate how VLGR1 participates in FA turnover. Nocodazole washout assays and live-cell imaging of RFP-paxillin consistently demonstrated that FA disassembly was not altered, de novo assembly of FA was significantly delayed in Vlgr1-deficient astrocytes indicating that VLGR1 is enrolled in the assembly of FAs. In FRAP experiments recovery rates were significantly reduced in Vlgr1-deficient FAs, indicating reduced turnover kinetics in VLGR1-deficient FAs. We showed that VLGR1 regulates cell migration by controlling the FA turnover during their assembly. From this, we expect novel insights into pathomechanisms related to pathogenic dysfunctions of VLGR1.
21 Dec 2022Submitted to Basic & Clinical Pharmacology & Toxicology
03 Jan 2023Review(s) Completed, Editorial Evaluation Pending
03 Jan 2023Submission Checks Completed
03 Jan 2023Assigned to Editor
03 Jan 2023Reviewer(s) Assigned
04 Feb 2023Editorial Decision: Revise Minor
15 Feb 20231st Revision Received
16 Feb 2023Submission Checks Completed
16 Feb 2023Assigned to Editor
16 Feb 2023Review(s) Completed, Editorial Evaluation Pending
17 Feb 2023Reviewer(s) Assigned
02 Mar 2023Editorial Decision: Revise Minor
08 Mar 20232nd Revision Received
09 Mar 2023Review(s) Completed, Editorial Evaluation Pending
09 Mar 2023Submission Checks Completed
09 Mar 2023Assigned to Editor
10 Mar 2023Editorial Decision: Accept