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

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 functi...

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Autores principales: Kusuluri, Deva K., Güler, Baran E., Knapp, Barbara, Horn, Nicola, Boldt, Karsten, Ueffing, Marius, Aust, Gabriela, Wolfrum, Uwe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024656/
https://www.ncbi.nlm.nih.gov/pubmed/33851099
http://dx.doi.org/10.1016/j.isci.2021.102283
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author Kusuluri, Deva K.
Güler, Baran E.
Knapp, Barbara
Horn, Nicola
Boldt, Karsten
Ueffing, Marius
Aust, Gabriela
Wolfrum, Uwe
author_facet Kusuluri, Deva K.
Güler, Baran E.
Knapp, Barbara
Horn, Nicola
Boldt, Karsten
Ueffing, Marius
Aust, Gabriela
Wolfrum, Uwe
author_sort Kusuluri, Deva K.
collection PubMed
description 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.
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spelling pubmed-80246562021-04-12 Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions Kusuluri, Deva K. Güler, Baran E. Knapp, Barbara Horn, Nicola Boldt, Karsten Ueffing, Marius Aust, Gabriela Wolfrum, Uwe iScience Article 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. Elsevier 2021-03-08 /pmc/articles/PMC8024656/ /pubmed/33851099 http://dx.doi.org/10.1016/j.isci.2021.102283 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Kusuluri, Deva K.
Güler, Baran E.
Knapp, Barbara
Horn, Nicola
Boldt, Karsten
Ueffing, Marius
Aust, Gabriela
Wolfrum, Uwe
Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions
title Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions
title_full Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions
title_fullStr Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions
title_full_unstemmed Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions
title_short Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions
title_sort adhesion g protein-coupled receptor vlgr1/adgrv1 regulates cell spreading and migration by mechanosensing at focal adhesions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024656/
https://www.ncbi.nlm.nih.gov/pubmed/33851099
http://dx.doi.org/10.1016/j.isci.2021.102283
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