The RGD motif in fibronectin is essential for development but dispensable for fibril assembly.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Takahashi, S; Leiss, M; Moser, M; Ohashi, T; Kitao, T; Heckmann, D; Pfeifer, A; Kessler, H; Takagi, J; Erickson, HP; Fässler, R
Published Date
- July 2, 2007
Published In
Volume / Issue
- 178 / 1
Start / End Page
- 167 - 178
PubMed ID
- 17591922
Pubmed Central ID
- PMC2064432
International Standard Serial Number (ISSN)
- 0021-9525
Digital Object Identifier (DOI)
- 10.1083/jcb.200703021
Language
- eng
Conference Location
- United States