Publications [#113235] of Harold P. Erickson

Papers Published

1. S Takahashi, M Leiss, M Moser, T Ohashi, T Kitao, D Heckmann, A Pfeifer, H Kessler, J Takagi, HP Erickson, R Fässler, The RGD motif in fibronectin is essential for development but dispensable for fibril assembly., The Journal of cell biology, vol. 178 no. 1 (July, 2007), pp. 167-78, ISSN 0021-9525
   (last updated on 2013/05/16)

   Abstract:
   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.

   Keywords:
   Amino Acid Motifs • Amino Acid Sequence • Amino Acid Substitution • Animals • Aspartic Acid • Binding Sites • Cell Line, Transformed • Dimerization • Disulfides • Embryo, Mammalian • Extracellular Matrix • Fibroblasts • Fibronectins • Heterozygote • Integrin alphaVbeta3 • Mice • Oligopeptides • Protein Binding • Protein Structure, Tertiary • Recombinant Proteins • Reticulin • Solubility • chemistry • chemistry* • cytology • genetics • metabolism • metabolism*