Invadosomes support cell invasion by coupling both acto-adhesive and extracellular matrix degradative functions, which are apparently antagonistic. β1-integrin dynamics regulate this coupling, but the actual sensing mechanism and effectors involved have not yet been elucidated. Using genetic and reverse genetic approaches combined with biochemical and imaging techniques, we now show that the calcium channel TRPV4 colocalizes with β1-integrins at the invadosome periphery and regulates its activation and the coupling of acto-adhesive and degradative functions. TRPV4-mediated regulation of podosome function depends on its ability to sense reactive oxygen species (ROS) in invadosomes’ microenvironment and involves activation of the ROS/calcium-sensitive kinase Ask1 and binding of the motor MYO1C. Furthermore, disease-associated TRPV4 gain-of-function mutations that modulate ECM degradation are also implicated in the ROS response, which provides new perspectives in our understanding of the pathophysiology of TRPV4 channelopathies.
Skip Nav Destination
Close
Article navigation
1 February 2021
Article|
January 05 2021
Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes
Sanela Vellino
,
Sanela Vellino
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Search for other works by this author on:
Christiane Oddou
,
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Search for other works by this author on:
Paul Rivier
,
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Search for other works by this author on:
Cyril Boyault
,
Cyril Boyault
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Search for other works by this author on:
Edwige Hiriart-Bryant
,
Edwige Hiriart-Bryant
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Search for other works by this author on:
Alexandra Kraut
,
Alexandra Kraut
2
Laboratoire EDyP, Institute of Biosciences and Biotechnologies of Grenoble-Biologie à Grande Echelle, Commissariat à l'Énergie Atomique Grenoble, Grenoble, France
Search for other works by this author on:
René Martin
,
René Martin
3
Faculty of Chemistry, Technische Universität Dresden, Dresden, Germany
Search for other works by this author on:
Yohann Coute
,
Yohann Coute
2
Laboratoire EDyP, Institute of Biosciences and Biotechnologies of Grenoble-Biologie à Grande Echelle, Commissariat à l'Énergie Atomique Grenoble, Grenoble, France
Search for other works by this author on:
Hans-Joachim Knölker
,
Hans-Joachim Knölker
3
Faculty of Chemistry, Technische Universität Dresden, Dresden, Germany
Search for other works by this author on:
Miguel A. Valverde
,
Miguel A. Valverde
4
Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
Search for other works by this author on:
Corinne Albigès-Rizo
,
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Search for other works by this author on:
Olivier Destaing
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Correspondence to Olivier Destaing: olivier.destaing@univ-grenoble-alpes.fr
Search for other works by this author on:
Sanela Vellino
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Christiane Oddou
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Paul Rivier
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Cyril Boyault
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Edwige Hiriart-Bryant
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Alexandra Kraut
2
Laboratoire EDyP, Institute of Biosciences and Biotechnologies of Grenoble-Biologie à Grande Echelle, Commissariat à l'Énergie Atomique Grenoble, Grenoble, France
René Martin
3
Faculty of Chemistry, Technische Universität Dresden, Dresden, Germany
Yohann Coute
2
Laboratoire EDyP, Institute of Biosciences and Biotechnologies of Grenoble-Biologie à Grande Echelle, Commissariat à l'Énergie Atomique Grenoble, Grenoble, France
Hans-Joachim Knölker
3
Faculty of Chemistry, Technische Universität Dresden, Dresden, Germany
Miguel A. Valverde
4
Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
Corinne Albigès-Rizo
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
Olivier Destaing
1
Dynamique des systèmes d'adhérence, Institut for Advanced Biosciences, Centre de Recherche University Grenoble Alpes/INSERM U1209/Centre National de la Recherche Scientifique Unité mixte de recherche 5309, La Tronche, France
**
C. Albigès-Rizo and O. Destaing contributed equally to this paper.
*
C. Oddou and P. Rivier contributed equally to this paper.
Correspondence to Olivier Destaing: olivier.destaing@univ-grenoble-alpes.fr
Received:
October 12 2019
Revision Received:
July 23 2020
Accepted:
November 13 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
Agence Nationale de la Recherche
(ANR-13-JSV2-0003-01)
European Regional Development Fund
(NO AWARD)
Fondation ARC pour la Recherche sur le Cancer
(NO AWARD)
H2020 Marie Skłodowska-Curie Actions
(ANR-10-INBS-08-01)
Ligue Contre le Cancer
(RTI2018-099718)
© 2021 Vellino et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (2): e201910079.
Article history
Received:
October 12 2019
Revision Received:
July 23 2020
Accepted:
November 13 2020
Citation
Sanela Vellino, Christiane Oddou, Paul Rivier, Cyril Boyault, Edwige Hiriart-Bryant, Alexandra Kraut, René Martin, Yohann Coute, Hans-Joachim Knölker, Miguel A. Valverde, Corinne Albigès-Rizo, Olivier Destaing; Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes. J Cell Biol 1 February 2021; 220 (2): e201910079. doi: https://doi.org/10.1083/jcb.201910079
Download citation file:
Close
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your Institution
505
Views
0
Citations
Advertisement
Advertisement