Proteoglycans are abundant on the surface of epidermal keratinocytes, but their function is unknown. Cell-cell adhesive interactions play a central role in normal and pathologic tissue organization. Epican, a newly discovered heparan sulfate form of CD44, has been found on keratinocytes and preliminary data indicate that epican could function as an adhesion molecule on keratinocytes.
The aims of this proposal are to: I. Dissect the molecular basis for epican-mediated keratinocyte- keratinocyte adhesion. We propose to a) determine the role in adhesion of hyaluronic acid, the covalently-linked heparan sulfate and the N- linked sugars; b) identify the binding site on the epican core protein either by creating deletion mutants of epican that prevent binding of transfectants to keratinocytes or by using panels of synthetic peptides and/or domain-specific monoclonal antibodies to block cell-cell adhesion; II. Determine the functional consequences of epican expression on keratinocytes. We propose to test the role of epican in a) cell-cell and cell-matrix adhesion b) growth regulation and c) cell and tissue morphology by overpressing epican in spontaneous keratinocyte lines that express low levels of epican. III. Determine that functional consequences of epican expression on melanocytes by examining a) the conditions under which epican is expressed on melanocytes; b) the effects of epican expression on growth, morphology and adhesive characteristics of melanocytes or melanoma cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR041478-01A1
Application #
2080747
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1993-12-07
Project End
1996-11-30
Budget Start
1993-12-07
Budget End
1994-11-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Yale University
Department
Dermatology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Herbold, K W; Zhou, J; Haggerty, J G et al. (1996) CD44 expression on epidermal melanocytes. J Invest Dermatol 106:1230-5