Alternative splicing of the angiogenesis associated extra-domain B of fibronectin regulates the accessibility of the B-C loop of the type III repeat 8

Elisa Ventura, Francesca Sassi, Arianna Parodi, Enrica Balza, Laura Borsi, Patrizia Castellani, Barbara Carnemolla, Luciano Zardi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Fibronectin (FN) is a multi-domain molecule involved in many cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. The biological activities of FN are mediated by exposed loops located mainly at the interdomain interfaces that interact with various molecules such as, but not only, integrins. Different FN isoforms arise from the alternative splicing of the pre-mRNA. In malignancies, the splicing pattern of FN pre-mRNA is altered; in particular, the FN isoform containing the extra-domain B (ED-B), a complete FN type III repeat constituted by 91 residues, is undetectable in normal adult tissues, but exhibits a much greater expression in fetal and tumor tissues, and is accumulated around neovasculature during angiogenic processes, thus making ED-B one of the best markers and targets of angiogenesis. The functions of ED-B are still unclear; however, it has been postulated that the insertion of an extra-domain such as ED-B modifies the domain-domain interface and may unmask loops that are otherwise cryptic, thus giving FN new potential activities. Methodology: We used the mAb C6, which reacts with ED-B containing FN, but not with ED-B-free FN and various recombinant FN fragments containing mutations, to precisely localize the epitopes recognized by the mAb C6. Conclusion: We formally demonstrated that the inclusion of the alternatively spliced angiogenesis-associated ED-B leads to the unmasking of the FNIII 8 B-C loop that is cryptic in FN molecules lacking ED-B. Thus, the mAb C6, in addition to providing a new reagent for angiogenesis targeting, represents a new tool for the study of the potential biological functions of the B-C loop of the repeat FNIII 8 that is unmasked during angiogenic processes.

Original languageEnglish
Article numbere9145
JournalPLoS One
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 10 2010

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fibronectins
alternative splicing
Alternative Splicing
angiogenesis
Fibronectins
RNA Precursors
Tissue
Molecules
Protein Isoforms
blood coagulation
integrins
Blood Coagulation
blood cells
Bioactivity
tissue repair
cell movement
Cell Adhesion
Integrins
epitopes
Embryonic Development

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Alternative splicing of the angiogenesis associated extra-domain B of fibronectin regulates the accessibility of the B-C loop of the type III repeat 8. / Ventura, Elisa; Sassi, Francesca; Parodi, Arianna; Balza, Enrica; Borsi, Laura; Castellani, Patrizia; Carnemolla, Barbara; Zardi, Luciano.

In: PLoS One, Vol. 5, No. 2, e9145, 10.02.2010.

Research output: Contribution to journalArticle

Ventura, Elisa ; Sassi, Francesca ; Parodi, Arianna ; Balza, Enrica ; Borsi, Laura ; Castellani, Patrizia ; Carnemolla, Barbara ; Zardi, Luciano. / Alternative splicing of the angiogenesis associated extra-domain B of fibronectin regulates the accessibility of the B-C loop of the type III repeat 8. In: PLoS One. 2010 ; Vol. 5, No. 2.
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