Molecular analysis of fibulin-5 function during De Novo synthesis of elastic fibers

Qian Zheng, Elaine C. Davis, James A. Richardson, Barry C. Starcher, Tiansen Li, Robert D. Gerard, Hiromi Yanagisawa

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Elastic fibers contribute to the structural support of tissues and to the regulation of cellular behavior. Mice deficient for the fibulin-5 gene (fbln5-/-) were used to further elucidate the molecular mechanism of elastic fiber assembly. Major elastic fiber components were present in the skin of fbln5-/- mice despite a dramatic reduction of mature elastic fibers. We found that fibulin-5 preferentially bound the monomeric form of elastin through N-terminal and C-terminal elastin-binding regions and to a preexisting matrix scaffold through calcium-binding epidermal growth factor (EGF)-like (CB-EGF) domains. We further showed that adenovirus-mediated gene transfer of fbln5 was sufficient to regenerate elastic fibers and increase elastic fiber-cell connections in vivo. A mutant fibulin-5 lacking the first 28 amino acids of the first CB-EGF domain, however, was unable to rescue elastic fiber defects. Fibulin-5 thus serves as an adaptor molecule between monomeric elastin and the matrix scaffold to aid in elastic fiber assembly. These results also support the potential use of fibulin-5 as a therapeutic agent for the treatment of elastinopathies.

Original languageEnglish (US)
Pages (from-to)1083-1095
Number of pages13
JournalMolecular and cellular biology
Volume27
Issue number3
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Zheng, Q., Davis, E. C., Richardson, J. A., Starcher, B. C., Li, T., Gerard, R. D., & Yanagisawa, H. (2007). Molecular analysis of fibulin-5 function during De Novo synthesis of elastic fibers. Molecular and cellular biology, 27(3), 1083-1095. https://doi.org/10.1128/MCB.01330-06