ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation

Ko Tsutsui, Ri Ichiroh Manabe, Tomiko Yamada, Itsuko Nakano, Yasuko Oguri, Douglas R. Keene, Gerhard Sengle, Lynn Sakai, Kiyotoshi Sekiguchi

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs)-like (ADAMTSL) proteins, a subgroup of the ADAMTS superfamily, share several domains with ADAMTS proteinases, including thrombospondin type I repeats, a cysteine-rich domain, and an ADAMTS spacer, but lack a catalytic domain. We identified two new members of ADAMTSL proteins, ADAMTSL-6α and -6β, that differ in their N-terminal amino acid sequences but have common C-terminal regions. When transfected into MG63 osteosarcoma cells, both isoforms were secreted and deposited into pericellular matrices, although ADAMTSL-6α, in contrast to -6β, was barely detectable in the conditioned medium. Immunolabeling at the light and electron microscopic levels showed their close association with fibrillin-1-rich microfibrils in elastic connective tissues. Surface plasmon resonance analyses demonstrated that ADAMTSL-6β binds to the N-terminal half of fibrillin-1 with a dissociation constant of ∼80 nM.WhenMG63cells were transfected or exogenously supplemented with ADAMTSL-6, fibrillin-1 matrix assembly was promoted in the early but not the late stage of the assembly process. Furthermore, ADAMTSL-6 transgenic mice exhibited excessive fibrillin-1 fibril formation in tissues where ADAMTSL-6 was overexpressed. All together, these results indicated that ADAMTSL-6 is a novel microfibril-associated protein that binds directly to fibrillin-1 and promotes fibrillin-1 matrix assembly.

Original languageEnglish (US)
Pages (from-to)4870-4882
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number7
DOIs
StatePublished - Feb 12 2010

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Thrombospondins
Disintegrins
Extracellular Matrix Proteins
Metalloproteases
Microfibrils
Fibrillin-1
Tissue
Amino Acid Motifs
Elastic Tissue
Surface Plasmon Resonance
Staphylococcal Protein A
Surface plasmon resonance
Osteosarcoma
Conditioned Culture Medium
Connective Tissue
Transgenic Mice
Cysteine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Tsutsui, K., Manabe, R. I., Yamada, T., Nakano, I., Oguri, Y., Keene, D. R., ... Sekiguchi, K. (2010). ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. Journal of Biological Chemistry, 285(7), 4870-4882. https://doi.org/10.1074/jbc.M109.076919

ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. / Tsutsui, Ko; Manabe, Ri Ichiroh; Yamada, Tomiko; Nakano, Itsuko; Oguri, Yasuko; Keene, Douglas R.; Sengle, Gerhard; Sakai, Lynn; Sekiguchi, Kiyotoshi.

In: Journal of Biological Chemistry, Vol. 285, No. 7, 12.02.2010, p. 4870-4882.

Research output: Contribution to journalArticle

Tsutsui, K, Manabe, RI, Yamada, T, Nakano, I, Oguri, Y, Keene, DR, Sengle, G, Sakai, L & Sekiguchi, K 2010, 'ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation', Journal of Biological Chemistry, vol. 285, no. 7, pp. 4870-4882. https://doi.org/10.1074/jbc.M109.076919
Tsutsui, Ko ; Manabe, Ri Ichiroh ; Yamada, Tomiko ; Nakano, Itsuko ; Oguri, Yasuko ; Keene, Douglas R. ; Sengle, Gerhard ; Sakai, Lynn ; Sekiguchi, Kiyotoshi. / ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 7. pp. 4870-4882.
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AU - Nakano, Itsuko

AU - Oguri, Yasuko

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