Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions

作者: Uwe Wolfrum , Gabriela Aust , Karsten Boldt , Nicola Horn , Barbara Knapp

DOI: 10.1016/J.ISCI.2021.102283

关键词: CellHaploinsufficiencyMetabotropic receptorCell biologyFocal adhesionReceptorG protein-coupled receptorInteractomeChemistryProteomics

摘要: Summary VLGR1 (very large G protein-coupled receptor-1) is by far the largest adhesion receptor in humans. Homozygous pathologic variants of cause hereditary deaf blindness Usher syndrome 2C and haploinsufficiency associated with epilepsy. However, its molecular function remains elusive. Herein, we used affinity proteomics to identify many components focal adhesions (FAs) interactome. localized FAs assembles FA protein complexes situ. Depletion or loss decreases number length hTERT-RPE1 cells astrocytes Vlgr1 mutant mice. depletion reduces cell spread migration kinetics as well response mechanical stretch characterizing a metabotropic mechanosensor FAs. Our data reveal critical role enlighten potential pathomechanisms diseases related VLGR1.

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