Protein-bound carbohydrates on cell-surface as targets of recognition: an odyssey in understanding them.

Abstract

Multidisciplinary approaches by a number of investigators have established that cell-surface carbohydrates are integral components of recognition systems regulating survival, migration, adhesion, growth and differentiation of various cells. Our own experience and contributions to this exciting field are described. We discovered Endo D as the first endoglycosidase acting on glycoproteins, found complementary specificity of two endoglycosidases (Endo D and Endo H), and applied these enzymes for glycoprotein research. Endo-beta-galactosidase C, which hydrolyzes Galalpha1-3Galbeta1-4GlcNAc xenoantigenic determinant, was later found and molecularly cloned. We also found highly branched poly-N-acetyllactosamines in early embryonic cells, and demonstrated developmentally regulated carbohydrate changes during early mammalian development. The binding site for Dolichos biflorus agglutinin was introduced as a new differentiation marker. Basigin and embigin, two related members of the immunoglobulin superfamily, a sialomucin MGC-24 and other glycoproteins were discovered as carriers of developmentally regulated carbohydrate markers. We proposed enhancement of integrin action as a function of sugar chains with Lewis X epitope, and observed a relationship between the expression of carbohydrate markers and invasive properties of human carcinoma. Midkine, a heparin-binding growth factor, was discovered more recently and its interaction with heparin and oversulfated chondroitin sulfate was elucidated. N-Acetylglucosamine-6-sulfotransferase was cloned and used to reconstitute L-selectin ligands. Gene knockout was applied to reveal in vivo function of basigin, syndecan-4 and chondroitin 6-sulfate. Throughout my research on all these subjects, I have been fortunate in obtaining unexpected observations and enjoying fruitful collaborations.