title: αvβ3 integrins negatively regulate cellular forces by phosphorylation of its distal NPXY site.
abstract: BACKGROUND
  Integrins are key receptors that allow cells to sense and respond to their mechanical environment. Although they bind the same ligand, β1 and β3 integrins have distinct and cooperative roles in mechanotransduction.
  
  
  RESULTS
  Using traction force microscopy on unconstrained cells, we show that deleting β3 causes traction forces to increase, whereas the deletion of β1 integrin results in a strong decrease of contractile forces. Consistently, loss of β3 integrin also induces an increase in β1 integrin activation. Using a genetic approach, we identified the phosphorylation of the distal NPXY domain as an essential process for β3 integrin to be able to modulate traction forces. Loss of β3 integrins also impacted cell shape and the spatial distribution of traction forces, by causing forces to be generated closer to the cell edge, and the cell shape.
  
  
  CONCLUSIONS
  Our results emphasize the role of β3 integrin in spatial distribution of cellular forces. We speculate that, by modulating its affinity with kindlin, β3 integrins may be able to locate near the cell edge where it can control β1 integrin activation and clustering.
  
  
  CONCLUSIONS
  Tensional homeostasis at the single cell level is performed by the ability of β3 adhesions to negatively regulate the activation degree and spatial localization of β1 integrins. By combining genetic approaches and new tools to analyze traction distribution and cell morphology on a population of cells we were able to identify the molecular partners involved in cellular forces regulation.
authors.affiliation: Laboratoire Interdisciplinaire de Physique, UMR CNRS 5588, Université Grenoble Alpes, Grenoble, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Milloud
authors.affiliation: Institute for Advanced Biosciences, Institut Albert Bonniot, Inserm U1209, CNRS 5309, Dynamique de l'adhérence cellulaire et de la différenciation, Université Grenoble Alpes, Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Destaing
authors.affiliation: Laboratoire Interdisciplinaire de Physique, UMR CNRS 5588, Université Grenoble Alpes, Grenoble, France.
authors.forename: Richard
authors.initials: R
authors.lastname: de Mets
authors.affiliation: Institute for Advanced Biosciences, Institut Albert Bonniot, Inserm U1209, CNRS 5309, Dynamique de l'adhérence cellulaire et de la différenciation, Université Grenoble Alpes, Grenoble, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bourrin-Reynard
authors.affiliation: Institute for Advanced Biosciences, Institut Albert Bonniot, Inserm U1209, CNRS 5309, Dynamique de l'adhérence cellulaire et de la différenciation, Université Grenoble Alpes, Grenoble, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Oddou
authors.affiliation: Laboratoire Interdisciplinaire de Physique, UMR CNRS 5588, Université Grenoble Alpes, Grenoble, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Delon
authors.affiliation: Laboratoire Interdisciplinaire de Physique, UMR CNRS 5588, Université Grenoble Alpes, Grenoble, France.
authors.forename: Irène
authors.initials: I
authors.lastname: Wang
authors.affiliation: Institute for Advanced Biosciences, Institut Albert Bonniot, Inserm U1209, CNRS 5309, Dynamique de l'adhérence cellulaire et de la différenciation, Université Grenoble Alpes, Grenoble, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Albigès-Rizo
authors.affiliation: Laboratoire Interdisciplinaire de Physique, UMR CNRS 5588, Université Grenoble Alpes, Grenoble, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Balland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001696:Biomechanical Phenomena; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000235:genetics* / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics* / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: D002352:Carrier Proteins; D039302:Integrin alphaVbeta3; D019012:Integrin beta1; D039661:Integrin beta3; C534220:kindlin-1 protein, mouse; D049452:Green Fluorescent Proteins
keywords: Cell adhesion; Cytoskeleton; Integrins