title: ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation.
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-6alpha and -6beta, 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-6alpha, in contrast to -6beta, 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-6beta binds to the N-terminal half of fibrillin-1 with a dissociation constant of approximately 80 nm. When MG63 cells 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.
authors: Sekiguchi Biomatrix Signaling Project, Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
authors: Ko
authors: K
authors: Tsutsui
authors: Ri-ichiroh
authors: R
authors: Manabe
authors: Tomiko
authors: T
authors: Yamada
authors: Itsuko
authors: I
authors: Nakano
authors: Yasuko
authors: Y
authors: Oguri
authors: Douglas R
authors: DR
authors: Keene
authors: Gerhard
authors: G
authors: Sengle
authors: Lynn Y
authors: LY
authors: Sakai
authors: Kiyotoshi
authors: K
authors: Sekiguchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D015139:Blotting, Southern; D002356:Cartilage / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line; D004622:Embryo, Mammalian / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D054392:Adipokines
chemical_list: D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D006023:Glycoproteins; D008840:Microfilament Proteins; C000605724:Fbn1 protein, mouse; D054392:Adipokines