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Post-translational processing of bovine chondromodulin-I
A Azizan1, N Holaday, P J Neame
1Center for Research in Skeletal Development and Pediatric Orthopedics, Shriners Hospital for Children, Tampa, Florida 33612, USA.
The Journal of Biological Chemistry
|April 27, 2001
Summary
Chondromodulin-I (ChM-I) processing involves intracellular cleavage by furin at a specific site, leading to rapid secretion of the mature glycopeptide. An additional extracellular processing event generates a smaller form observed only in cartilage.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Chondromodulin-I (ChM-I) is a glycoprotein abundant in fetal cartilage.
- Mature ChM-I is derived from a larger precursor through proteolytic processing.
- Understanding ChM-I processing is crucial for cartilage biology and development.
Purpose of the Study:
- To elucidate the processing pathway and identify the enzymes involved in ChM-I maturation.
- To investigate the intracellular and extracellular events governing ChM-I processing.
- To determine the role of specific cleavage sites and cellular machinery in ChM-I processing.
Main Methods:
- Utilized antipeptide antisera to identify precursor, mature, and processed forms of ChM-I.
- Employed cultured chondrocytes, chondrosarcoma cells, and transfected Chinese hamster ovary (CHO) cells.
- Performed pulse-chase analysis and site-directed mutagenesis of the ChM-I precursor cleavage site.
- Expressed ChM-I in furin-deficient CHO cells to assess furin's role.
Main Results:
- ChM-I precursor is processed intracellularly at the RERR-ELVR site, likely by furin.
- Mature ChM-I is rapidly secreted post-cleavage.
- A smaller, unglycosylated form of ChM-I is generated through an extracellular event, observed specifically in cartilage.
- Mutating the cleavage site or using furin-deficient cells abolished processing.
Conclusions:
- ChM-I processing is a multi-step event involving intracellular furin-mediated cleavage and subsequent extracellular modifications.
- The rapid secretion of mature ChM-I suggests it is not a juxtacrine growth factor.
- The distinct processing pathways highlight tissue-specific modifications of ChM-I.
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