The adhesion GPCR VLGR1/ADGRV1 regulates focal adhesion turnover by
controlling their assembly
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.