| First Author | Takahashi S | Year | 2007 |
| Journal | J Cell Biol | Volume | 178 |
| Issue | 1 | Pages | 167-78 |
| PubMed ID | 17591922 | Mgi Jnum | J:177821 |
| Mgi Id | MGI:5296311 | Doi | 10.1083/jcb.200703021 |
| Citation | Takahashi S, et al. (2007) The RGD motif in fibronectin is essential for development but dispensable for fibril assembly. J Cell Biol 178(1):167-78 |
| abstractText | Fibronectin (FN) is secreted as a disulfide-bonded FN dimer. Each subunit contains three types of repeating modules: FN-I, FN-II, and FN-III. The interactions of alpha5beta1 or alphav integrins with the RGD motif of FN-III repeat 10 (FN-III10) are considered an essential step in the assembly of FN fibrils. To test this hypothesis in vivo, we replaced the RGD motif with the inactive RGE in mice. FN-RGE homozygous embryos die at embryonic day 10 with shortened posterior trunk, absent tail bud-derived somites, and severe vascular defects resembling the phenotype of alpha5 integrin-deficient mice. Surprisingly, the absence of a functional RGD motif in FN did not compromise assembly of an FN matrix in mutant embryos or on mutant cells. Matrix assembly assays and solid-phase binding assays reveal that alphavbeta3 integrin assembles FN-RGE by binding an isoDGR motif in FN-I5, which is generated by the nonenzymatic rearrangement of asparagines (N) into an iso-aspartate (iso-D). Our findings demonstrate that FN contains a novel motif for integrin binding and fibril formation whose activity is controlled by amino acid modification. |
