This project addresses the biochemical mechanism which regulates proteoglycan chain specific glycosaminoglycan modification. Three proteoglycan and their core proteins will be studied (aggrecan, biglycan and decorin) using an immortalized clonal mouse chondrocyte cell line that reproduces the core-specific epimerization observed in cartilage in vivo. The distinctive functions of dermatan sulfate proteoglycans in regulation of collagen fibrillogenesis, compared with that for space filling and water retaining form such as aggrecan, justify efforts here to understand the process controlling their biosynthesis. These studies arise from the hypothesis that both the initiation and extent of epimerization is regulated by selective protein-protein interactions of proteoglycan core proteins with intra-Golgi proteins during glycosaminoglycan biosynthesis.
The specific aims are : 1) to use intra Golgi cross-linking and affinity chromatography on core protein-derivatized support to determine whether core proteins of aggrecan, decorin, and biglycan interact with specific sets of intra-Golgi proteins; and 2) to assess the feasibility for an innovative approach to characterize the microenvironment of core proteins within the Golgi apparatus by the immunoisolation of Golgi-derived vesicles that contain aggrecan, decorin, or biglycan. These studies are expected to enhance understanding of epimerization of dermatan sulfate which may impact other research areas through characterization of a novel regulatory mechanism in proteoglycan biosynthesis and of novel processes in Golgi trafficking and sorting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
7R03DE012652-02
Application #
2791552
Study Section
NIDCR Special Grants Review Committee (DSR)
Project Start
1998-03-01
Project End
2000-02-29
Budget Start
1998-06-01
Budget End
1999-02-28
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260