摘要：SummaryVLGR1 (very large G protein-coupled receptor-1) is by far the largest adhesion G protein-coupled receptor in humans. Homozygous pathologic variants ofVLGR1cause hereditary deaf blindness in Usher syndrome 2C and haploinsufficiency ofVLGR1is associated with epilepsy. However, its molecular function remains elusive. Herein, we used affinity proteomics to identify many components of focal adhesions (FAs) in the VLGR1 interactome. VLGR1 is localized in FAs and assembles in FA protein complexesin situ. Depletion or loss of VLGR1 decreases the number and length of FAs in hTERT-RPE1 cells and in astrocytes ofVlgr1mutant mice. VLGR1 depletion reduces cell spread and migration kinetics as well as the response to mechanical stretch characterizing VLGR1 as a metabotropic mechanosensor in FAs. Our data reveal a critical role of VLGR1 in the FA function and enlighten potential pathomechanisms in diseases related to VLGR1.Graphical abstractDisplay OmittedHighlights•VLGR1 is an integral part of focal adhesions and crucial for their assembly•Absence of VLGR1 from focal adhesions alters cell spreading and cell migration•VLGR1 is a metabotropic mechanosensor in focal adhesionsBiomolecules; Molecular Biology; Cell Biology
