| First Author | Zou W | Year | 2015 |
| Journal | J Cell Biol | Volume | 208 |
| Issue | 1 | Pages | 125-36 |
| PubMed ID | 25547154 | Mgi Jnum | J:233352 |
| Mgi Id | MGI:5781288 | Doi | 10.1083/jcb.201410123 |
| Citation | Zou W, et al. (2015) Absence of Dap12 and the alphavbeta3 integrin causes severe osteopetrosis. J Cell Biol 208(1):125-36 |
| abstractText | In vitro, ligand occupancy of alphavbeta3 integrin induces phosphorylation of Dap12, which is essential for osteoclast function. Like mice deleted of only alphavbeta3, Dap12(-/-) mice exhibited a slight increase in bone mass, but Dap12(-/-) mice, lacking another ITAM protein, FcRgamma, were severely osteopetrotic. The mechanism by which FcRgamma compensates for Dap12 deficiency is unknown. We find that co-deletion of FcRgamma did not exacerbate the skeletal phenotype of beta3(-/-) mice. In contrast, beta3/Dap12 double-deficient (DAP/beta3(-/-)) mice (but not beta1/Dap12 double-deficient mice) were profoundly osteopetrotic, reflecting severe osteoclast dysfunction relative to those lacking alphavbeta3 or Dap12 alone. Activation of OSCAR, the FcRgamma co-receptor, rescued Dap12(-/-) but not DAP/beta3(-/-)osteoclasts. Thus, the absence of alphavbeta3 precluded compensation for Dap12 deficiency by FcRgamma. In keeping with this, Syk phosphorylation did not occur in OSCAR-activated DAP/beta3(-/-) osteoclasts. Thus, FcRgamma requires the osteoclast alphavbeta3 integrin to normalize the Dap12-deficient skeleton. |
