The glycosaminoglycan components of proteoglycans are biosynthesized and modified in the golgi apparatus by highly organized carbohydrate transfer enzymes and sulfotransferases. The purpose of this project is to investigate the functional organization and subcellular localization of these enzyme complexes. Brefeldin A is a chemical which specifically blocks anterograde protein transport within the golgi apparatus. It was used to disrupt the normal biosynthetic processes for adding glycosaminoglycan chains onto proteoglycans. When ovarian granulosa cells were treated with Brefeldin A, dermatan sulfate proteoglycan synthesis was abolished whereas heparan sulfate proteoglycan synthesis was only partially inhibited, suggesting that dermatan sulfate and heparan sulfate assembly on proteoglycans occurs in different subcellular compartments. The finding that only normal heparan sulfate protein core proteins were substituted with heparan sulfate chains in the presence of the drug indicated that glycosylation enzymes are highly specific to core proteins. Topics of present interest include elucidation of core protein structure which determines highly specific glycosylation enzymes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000548-03
Application #
3753571
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code