Article
- The EMBO Journal (2007) 26, 3283 - 3295
- doi:10.1038/sj.emboj.7601768
Published online: 21 June 2007
Subject Category:
Latent TGF-
-binding protein 2 binds to DANCE/fibulin-5 and regulates elastic fiber assembly
Maretoshi Hirai1,2,a, Masahito Horiguchi1,2,a, Tetsuya Ohbayashi1, Toru Kita2, Kenneth R Chien3 and Tomoyuki Nakamura1,4
- Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
- Department of Pharmacology, Kansai Medical University, Osaka, Japan
Correspondence to:
Tomoyuki Nakamura, Department of Pharmacology, Kansai Medical University, 10-15, Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan. Tel.: +81 6 6993 9427; Fax: +81 6 6993 9428; E-mail: nakamtom@takii.kmu.ac.jp
aThese authors contributed equally to this work
Received 23 January 2007; Accepted 21 May 2007
Abstract
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-
-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.
Keywords:
- DANCE,
- elastic fiber,
- fibulin-5,
- LTBP-2,
- microfibril
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