title: Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis.
abstract: The amino and carboxyl propeptides of procollagens I and II are removed by specific enzymes as a prerequisite for fibril assembly. Null mutations in procollagen I N-propeptidase (ADAMTS-2) cause dermatosparaxis in cattle and the Ehlers-Danlos syndrome (dermatosparactic type) in humans by preventing proteolytic excision of the N-propeptide of procollagen I. We have found that procollagen II is processed normally in dermatosparactic nasal cartilage, suggesting the existence of another N-propeptidase(s). We investigated such a role for ADAMTS-3 in Swarm rat chondrosarcoma RCS-LTC cells, which fail to process the procollagen II N-propeptide. Stable transfection of RCS-LTC cells with bovine ADAMTS-2 or human ADAMTS-3 partially rescued the processing defect, suggesting that ADAMTS-3 has procollagen II N-propeptidase activity. Human skin and skin fibroblasts showed 30-fold higher mRNA levels of ADAMTS-2 than ADAMTS-3, whereas ADAMTS-3 mRNA was 5-fold higher than ADAMTS-2 mRNA in human cartilage. We propose that both ADAMTS-2 and ADAMTS-3 process procollagen II, but ADAMTS-3 is physiologically more relevant, given its preferred expression in cartilage. The findings provide an explanation for the sparing of cartilage in dermatosparaxis and, perhaps, for the relative sparing of some procollagen I-containing tissues.
authors.affiliation: Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington 98195-6500, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Fernandes
authors.forename: S
authors.initials: S
authors.lastname: Hirohata
authors.forename: J M
authors.initials: JM
authors.lastname: Engle
authors.forename: A
authors.initials: A
authors.lastname: Colige
authors.forename: D H
authors.initials: DH
authors.lastname: Cohn
authors.forename: D R
authors.initials: DR
authors.lastname: Eyre
authors.forename: S S
authors.initials: SS
authors.lastname: Apte
mesh_terms: D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D000071121:ADAMTS4 Protein; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology*; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000737:chemistry / Q000235:genetics; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D010446:Peptide Fragments; D011347:Procollagen; C109195:procollagen type IIA amino-terminal peptide; D010450:Endopeptidases; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C434951:ADAMTS3 protein, human; C000609307:ADAMTS2 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein