Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions
Deva K. Kusuluri,
Baran E. Güler,
Barbara Knapp,
Nicola Horn,
Karsten Boldt,
Marius Ueffing,
Gabriela Aust,
Uwe Wolfrum
Affiliations
Deva K. Kusuluri
Institute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University, Hanns-Dieter-Hüsch-Weg 17, 55099 Mainz, Germany
Baran E. Güler
Institute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University, Hanns-Dieter-Hüsch-Weg 17, 55099 Mainz, Germany
Barbara Knapp
Institute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University, Hanns-Dieter-Hüsch-Weg 17, 55099 Mainz, Germany
Nicola Horn
Medical Proteome Center, Institute for Ophthalmic Research, Eberhard Karls University of Tuebingen, 72074 Tuebingen, Germany
Karsten Boldt
Medical Proteome Center, Institute for Ophthalmic Research, Eberhard Karls University of Tuebingen, 72074 Tuebingen, Germany
Marius Ueffing
Medical Proteome Center, Institute for Ophthalmic Research, Eberhard Karls University of Tuebingen, 72074 Tuebingen, Germany
Gabriela Aust
Clinic of Visceral, Transplantation, Thoracic and Vascular Surgery & Clinic of Orthopedics, Traumatology and Plastic Surgery, Department of Surgery Research Laboratory, Leipzig University, 04301 Leipzig, Germany
Uwe Wolfrum
Institute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University, Hanns-Dieter-Hüsch-Weg 17, 55099 Mainz, Germany; Corresponding author
Summary: VLGR1 (very large G protein-coupled receptor-1) is by far the largest adhesion G protein-coupled receptor in humans. Homozygous pathologic variants of VLGR1 cause hereditary deaf blindness in Usher syndrome 2C and haploinsufficiency of VLGR1 is 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 complexes in situ. Depletion or loss of VLGR1 decreases the number and length of FAs in hTERT-RPE1 cells and in astrocytes of Vlgr1 mutant 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.
