Abstract
How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional analysis of β1- and αv-class integrins expressed in pan-integrin-null fibroblasts seeded on fibronectin. Reconstitution with β1-class integrins promotes myosin-II-independent formation of small peripheral adhesions and cell protrusions, whereas expression of αv-class integrins induces the formation of large focal adhesions. Co-expression of both integrin classes leads to full myosin activation and traction-force development on stiff fibronectin-coated substrates, with αv-class integrins accumulating in adhesion areas exposed to high traction forces. Quantitative proteomics linked αv-class integrins to a GEF-H1-RhoA pathway coupled to the formin mDia1 but not myosin II, and α5β1 integrins to a RhoA-Rock-myosin II pathway. Our study assigns specific functions to distinct fibronectin-binding integrins, demonstrating that α5β1integrins accomplish force generation, whereas αv-class integrins mediate the structural adaptations to forces, which cooperatively enable cells to sense the rigidity of fibronectin-based microenvironments.
| Original language | English |
|---|---|
| Journal | Nature Cell Biology |
| Volume | 15 |
| Issue number | 6 |
| Pages (from-to) | 625-36 |
| Number of pages | 12 |
| ISSN | 1465-7392 |
| DOIs | |
| Publication status | Published - Jun 2013 |
| Externally published | Yes |
Keywords
- Animals
- Antigens, CD29
- Carrier Proteins
- Cell Adhesion
- Cell Line
- Cell Movement
- Cellular Microenvironment
- Extracellular Matrix
- Extracellular Matrix Proteins
- Fibroblasts
- Fibronectins
- Focal Adhesions
- Guanine Nucleotide Exchange Factors
- Integrin alpha5beta1
- Integrin alphaV
- Male
- Mice
- Mice, Transgenic
- Myosin Type II
- Protein Binding
- Protein-Serine-Threonine Kinases
- Proto-Oncogene Proteins
- RNA Interference
- RNA, Small Interfering
- rho-Associated Kinases
- rhoA GTP-Binding Protein