Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis

Russell J. Fernandes, Satoshi Hirohata, J. Michael Engle, Alain Colige, Daniel H. Cohn, David R. Eyre, Suneel S. Apte

Research output: Contribution to journalArticle

171 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)31502-31509
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number34
DOIs
Publication statusPublished - Aug 24 2001
Externally publishedYes

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Procollagen
Cartilage
Processing
Messenger RNA
Skin
Nasal Cartilages
Ehlers-Danlos Syndrome
Chondrosarcoma
Ehlers-Danlos Syndrome, Type VII, Autosomal Recessive
Fibroblasts
Transfection
Rats
Tissue
Defects
Mutation
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fernandes, R. J., Hirohata, S., Engle, J. M., Colige, A., Cohn, D. H., Eyre, D. R., & Apte, S. S. (2001). Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis. Journal of Biological Chemistry, 276(34), 31502-31509. https://doi.org/10.1074/jbc.M103466200

Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis. / Fernandes, Russell J.; Hirohata, Satoshi; Engle, J. Michael; Colige, Alain; Cohn, Daniel H.; Eyre, David R.; Apte, Suneel S.

In: Journal of Biological Chemistry, Vol. 276, No. 34, 24.08.2001, p. 31502-31509.

Research output: Contribution to journalArticle

Fernandes, RJ, Hirohata, S, Engle, JM, Colige, A, Cohn, DH, Eyre, DR & Apte, SS 2001, 'Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis', Journal of Biological Chemistry, vol. 276, no. 34, pp. 31502-31509. https://doi.org/10.1074/jbc.M103466200
Fernandes, Russell J. ; Hirohata, Satoshi ; Engle, J. Michael ; Colige, Alain ; Cohn, Daniel H. ; Eyre, David R. ; Apte, Suneel S. / Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 34. pp. 31502-31509.
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