This proposal describes a plan to study how the molecular structure of CD44, a protein expressed on leukocytes and important in signalling and adhesion, is related to its function. The project involves the generation of multiple cDNAs of CD44 isoforms, the transfection of cells with each of these cDNAs, and analyses of consequent cell behavior. Post-translational modifications of CD44, primarily in the form of glycosylation, apparently affect the binding specificity for the protein. This project also focuses on changes in the glycosylation in the various isoforms of CD44, and the consequent changes in adhesion functions for the molecule. %%% The interaction of endothelial cell glycoproteins and their complementary leukocyte receptors directs the extravasation of lymphocytes into inflammatory sites. CD44 is the principal receptor for hyaluronic acid, is constitutively expressed on leukocytes, and mediates both intercellular attachment and extracellular matrix adhesion. CD44 also interacts with intracellular cytoskeletal elements, and thus, may provide an important link in coordinating extracellular attachments and subsequent changes in intracellular organization. The glycosylation of CD44 appears to play an important role in the binding specificity for the protein. Functional comparisons of various isoforms of CD44 with differing glycosylation patterns will provide information on the mechanism by which leukocytes migrate and insight into the events that transduce information from the extracellular environment into coordinated cellular movements.
