Article ; Online: Monitoring paxillin in astrocytes reveals the significance of the adhesion G protein coupled receptor VLGR1/ADGRV1 for focal adhesion assembly.
Basic & clinical pharmacology & toxicology
2023 Volume 133, Issue 4, Page(s) 301–312
Abstract: VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhesion G protein-coupled receptor (aGPCR). Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome, the most common form of deaf-blindness, and also with epilepsy in ... ...
| Abstract | VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhesion G protein-coupled receptor (aGPCR). Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome, the most common form of deaf-blindness, and also with epilepsy in humans and mice. VLGR1 is expressed almost ubiquitously but is mainly found in the CNS and in the sensory cells of the eye and inner ear. Little is known about the pathogenesis of the diseases related to VLGR1. We previously identified VLGR1 as a vital component of focal adhesions (FAs) serving as a metabotropic mechanoreceptor controls cell spreading and migration. FAs are highly dynamic and turnover in response to internal and external signals. Here, we aimed to elucidate how VLGR1 participates in FA turnover. Nocodazole washouts and live cell imaging of paxillin-DsRed2 consistently showed that FA disassembly was not altered, but de novo assembly of FA was significantly delayed in Vlgr1-deficient astrocytes, indicating that VLGR1 is enrolled in FA assembly. 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 and expect novel insights into pathomechanisms related to pathogenic dysfunctions of VLGR1. |
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| MeSH term(s) | Animals ; Humans ; Mice ; Paxillin/genetics ; Paxillin/metabolism ; Focal Adhesions/genetics ; Focal Adhesions/metabolism ; Astrocytes/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Cell Movement |
| Chemical Substances | Paxillin ; Receptors, G-Protein-Coupled |
| Language | English |
| Publishing date | 2023-03-30 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2134679-3 |
| ISSN | 1742-7843 ; 1742-7835 |
| ISSN (online) | 1742-7843 |
| ISSN | 1742-7835 |
| DOI | 10.1111/bcpt.13860 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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