Latent TGF-beta-binding protein 2 binds to DANCE/fibulin-5 and regulates elastic fiber assembly.
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-beta-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.
Hirai
Maretoshi
M
Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Horiguchi
Masahito
M
Ohbayashi
Tetsuya
T
Kita
Toru
T
Chien
Kenneth R
KR
Nakamura
Tomoyuki
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D004547:Elastic Tissue / Q000378:metabolism*; D004549:Elastin / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020894:Microfibrils / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012984:Software; D020349:Surface Plasmon Resonance; D054392:Adipokines
D002118:Calcium; D004549:Elastin; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; C492373:FBLN5 protein, human; C000605722:FBN1 protein, human; D054392:Adipokines; C120769:Fbln5 protein, mouse; C000605724:Fbn1 protein, mouse