Monitoring paxillin in astrocytes reveals the significance of the adhesion G protein coupled receptor VLGR1/ADGRV1 for focal adhesion assembly
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Abstract
VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhe sion 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 partici pates 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, indicat ing 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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Basic & clinical pharmacology & toxicology, Version of Record (VoR), Wiley-Blackwell, Oxford, 2023, https://doi.org/10.1111/bcpt.13860