Specialization of cell surfaces are an essential feature during differentiation. It is likely that a detailed appreciation of the structure and function of plasma membranes at the molecular level will promote our understanding of these alterations and their role in development. Towards this end, we have been investigating a mechanism for localizing developmental-stage specific glycoproteins at the cell periphery where they participate in tissue-specific metabolic processes, the extracellular hydrolysis of neural-transmitters and nutritive materials, as well as, intracellular adhesion. This mechanism utilizes an endogeneous membrane-bound receptor ligatin that recognizes a defined post-translational modification common to each ligatin-associated glycoprotein. We propose that differences in synthesis of these glycoproteins during cellular differentiation results in changes in function of the cell surface without necessitating changes in the receptor. Furthermore, because of ligatin's polymeric properties, binding of these effector molecules to ligatin for their localization at the cell surface constricts them to a discrete region of membrane in high concentration. We have evidence of the biological function of ligatin and now want an understanding in molecular terms of the material called ligatin and its binding properties. The proposed research is comprised of two projects. (1) We have recently demonstrated that ligatin purified to homogeneity is a proteo-lipid and have developed techniques for the separation of its components. We shall now complete the identification of these components and explore their individual roles in the biological function of ligatin. (2) We shall establish the degree to which homogeneous preparations of developmental-stage specific hydrolases bind to ligatin and examine the binding of glycopeptides and oligosaccharides derived from these ligatin-associated glycoproteins to identify ligatin's binding specificities.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM033529-04
Application #
3283375
Study Section
Biochemistry Study Section (BIO)
Project Start
1984-04-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705