| First Author | Batra N | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 9 | Pages | 3359-64 |
| PubMed ID | 22331870 | Mgi Jnum | J:181983 |
| Mgi Id | MGI:5314545 | Doi | 10.1073/pnas.1115967109 |
| Citation | Batra N, et al. (2012) Mechanical stress-activated integrin alpha5beta1 induces opening of connexin 43 hemichannels. Proc Natl Acad Sci U S A 109(9):3359-64 |
| abstractText | The connexin 43 (Cx43) hemichannel (HC) in the mechanosensory osteocytes is a major portal for the release of factors responsible for the anabolic effects of mechanical loading on bone formation and remodeling. However, little is known about how the Cx43 molecule responds to mechanical stimulation leading to the opening of the HC. Here, we demonstrate that integrin alpha5beta1 interacts directly with Cx43 and that this interaction is required for mechanical stimulation-induced opening of the Cx43 HC. Direct mechanical perturbation via magnetic beads or conformational activation of integrin alpha5beta1 leads to the opening of the Cx43 HC, and this role of the integrin is independent of its association with an extracellular fibronectin substrate. PI3K signaling is responsible for the shear stress-induced conformational activation of integrin alpha5beta1 leading to the opening of the HC. These results identify an unconventional function of integrin that acts as a mechanical tether to induce opening of the HC and provide a mechanism connecting the effect of mechanical forces directly to anabolic function of the bone. |
