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Latent TGF‐β‐binding protein 2 binds to DANCE/fibulin‐5 and regulates elastic fiber assembly
Author(s) -
Hirai Maretoshi,
Horiguchi Masahito,
Ohbayashi Tetsuya,
Kita Toru,
Chien Kenneth R,
Nakamura Tomoyuki
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601768
Subject(s) - biology , fibulin , microbiology and biotechnology , transforming growth factor , dance , plasma protein binding , fiber , extracellular matrix , materials science , art , literature , composite material
Elastic fibers play the principal roles in providing elasticity and integrity to various types of human organs, such as the arteries, lung, and skin. However, the molecular mechanism of elastic fiber assembly that leads to deposition and crosslinking of elastin along microfibrils remains largely unknown. We have previously shown that developing arteries and neural crest EGF‐like protein (DANCE) (also designated fibulin‐5) is essential for elastogenesis by studying DANCE‐deficient mice. Here, we report the identification of latent transforming growth factor‐β‐binding protein 2 (LTBP‐2), an elastic fiber‐associating protein whose function in elastogenesis is not clear, as a DANCE‐binding protein. Elastogenesis assays using human skin fibroblasts reveal that fibrillar deposition of DANCE and elastin is largely dependent on fibrillin‐1 microfibrils. However, downregulation of LTBP‐2 induces fibrillin‐1‐independent fibrillar deposition of DANCE and elastin. Moreover, recombinant LTBP‐2 promotes deposition of DANCE onto fibrillin‐1 microfibrils. These results suggest a novel regulatory mechanism of elastic fiber assembly in which LTBP‐2 regulates targeting of DANCE on suitable microfibrils to form elastic fibers.