Mammalian BMP-1/Tolloid-Related Metalloproteinases, Including Novel Family Member Mammalian Tolloid-Like 2, Have Differential Enzymatic Activities and Distributions of Expression Relevant to Patterning and Skeletogenesis

Vertebrate bone morphogenetic protein 1 (BMP-1) and Drosophila Tolloid (TLD) are prototypes of a family of metalloproteases with important roles in various developmental events. BMP-1 affects morphogenesis, at least partly, via biosynthetic processing of fibrillar collagens, while TLD affects dorsal...

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Bibliographic Details
Published in:Developmental biology 1999-09, Vol.213 (2), p.283-300
Main Authors: Scott, Ian C., Blitz, Ira L., Pappano, William N., Imamura, Yasutada, Clark, Timothy G., Steiglitz, Barry M., Thomas, Christina L., Maas, Sarah A., Takahara, Kazuhiko, Cho, Ken W.Y., Greenspan, Daniel S.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
astacin metalloprotease
BMP signaling
Body Patterning - genetics
Bone and Bones - embryology
Bone and Bones - physiology
Bone Morphogenetic Protein 1
Bone Morphogenetic Proteins - genetics
Bone Morphogenetic Proteins - metabolism
Chordin
Cloning, Molecular
Drosophila Proteins
Enzyme Activation
Glycoproteins - metabolism
Humans
Insect Proteins - genetics
Insect Proteins - metabolism
Intercellular Signaling Peptides and Proteins
Metalloendopeptidases - genetics
Metalloendopeptidases - metabolism
Mice
Molecular Sequence Data
osteogenesis
patterning
Sequence Alignment
Tolloid-Like Metalloproteinases
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Summary:Vertebrate bone morphogenetic protein 1 (BMP-1) and Drosophila Tolloid (TLD) are prototypes of a family of metalloproteases with important roles in various developmental events. BMP-1 affects morphogenesis, at least partly, via biosynthetic processing of fibrillar collagens, while TLD affects dorsal–ventral patterning by releasing TGFβ-like ligands from latent complexes with the secreted protein Short Gastrulation (SOG). Here, in a screen for additional mammalian members of this family of developmental proteases, we identify novel family member mammalian Tolloid-like 2 (mTLL-2) and compare enzymatic activities and expression domains of all four known mammalian BMP-1/TLD-like proteases [BMP-1, mammalian Tolloid (mTLD), mammalian Tolloid-like 1 (mTLL-1), and mTLL-2]. Despite high sequence similarities, distinct differences are shown in ability to process fibrillar collagen precursors and to cleave Chordin, the vertebrate orthologue of SOG. As previously demonstrated for BMP-1 and mTLD, mTLL-1 is shown to specifically process procollagen C-propeptides at the physiologically relevant site, while mTLL-2 is shown to lack this activity. BMP-1 and mTLL-1 are shown to cleave Chordin, at sites similar to procollagen C-propeptide cleavage sites, and to counteract dorsalizing effects of Chordin upon overexpression in Xenopus embryos. Proteases mTLD and mTLL-2 do not cleave Chordin. Differences in enzymatic activities and expression domains of the four proteases suggest BMP-1 as the major Chordin antagonist in early mammalian embryogenesis and in pre- and postnatal skeletogenesis.
ISSN:0012-1606
1095-564X
DOI:10.1006/dbio.1999.9383