The Biosynthesis of Membrane Glycoproteins: the Work of William J. Lennarz

Abstract

Membrane Glycoproteins. I. Enzymatic Synthesis of Mannosyl Phosphoryl Polyisoprenol and Its Role as a Mannosyl Donor in Glycoprotein Synthesis (Waechter, C. J., Lucas, J. J., and Lennarz, W. J. (1973) J. Biol. Chem. 248, 7570–7579) William Joseph Lennarz was born in New York City in 1934. He received his B.S. in chemistry from Pennsylvania State University in 1956 and his Ph.D. in organic chemistry from the University of Illinois in 1959. Subsequently, he carried out postdoctoral research on fatty acid biosynthesis at Harvard University with Journal of Biological Chemistry (JBC) Classic author Konrad Bloch (1.JBC Classics: Bloch, K., and Rittenberg, D. (1942) J. Biol. Chem. 145, 625–636; Rittenberg, D., and Bloch, K. (1945) J. Biol. Chem. 160, 417–424; Bloch, K. (1945) J. Biol. Chem. 157, 661–666 (http://www.jbc.org/cgi/content/full/280/10/e7)Google Scholar). In 1962 Lennarz moved to Baltimore where he was appointed Assistant Professor in the Department of Physiological Chemistry at the Johns Hopkins School of Medicine. He was later promoted to Associate Professor of Biochemistry in 1966 and Professor in 1971. The focus of Lennarz's work at Johns Hopkins was lipids and bacterial cell surfaces. He found that mannosyl phosphoryl undecaprenol participates in the biosynthesis of mannolipids in Micrococcus lysodeikticus (2.Lahav M. Chiu T.H. Lennarz W.J. Studies on the biosynthesis of mannan in Micrococcus lysodeikticus. II. The enzymatic synthesis of mannosyl-1-phosphoryl-undecaprenol.J. Biol. Chem. 1969; 244: 5890-5898Abstract Full Text PDF PubMed Google Scholar). This work showed that lipid-linked sugars were biosynthetic precursors of envelope-associated bacterial polysaccharides. Curious as to whether polyisoprenol phosphates also served as glycosyl carriers in mammalian tissue, Lennarz and his colleagues looked at the enzymatic transfer of mannose from GDP-mannose to endogenous acceptors in cell-free preparations of bovine thyroid and hen oviduct. This is the subject of the JBC Classic reprinted here. Lennarz found that the preparations did catalyze the transfer of mannose to several endogenous acceptors including mannosyl phosphoryl polyisoprenol. Two other receptors were discovered and named “soluble mannosylated endogenous acceptor” (mannosyl s-acceptor) and “residual mannosylated endogenous acceptor” (mannosyl r-acceptor). Lennarz and his colleagues then showed that mannosyl phosphoryl polyisoprenol serves as the mannosyl donor for the synthesis of both mannosyl s- and r-acceptor. He further postulated that mannosyl s-acceptor mediates the transfer of mannosyl residues from mannosyl phosphoryl polyisoprenol to glycoproteins. From these results Lennarz concludes, “it seems possible that in eukaryotic systems, as in bacterial systems, activated lipid-linked sugars mediate the synthesis of glycose-containing macro-molecules that are associated with the membranous components of the cell.” Lennarz left Baltimore for Texas in 1983 when he was appointed Robert A. Welch Professor and Chairman of the Department of Biochemistry and Molecular Biology at the University of Texas Cancer Center, M. D. Anderson Hospital in Houston. In 1989, he joined the faculty of the State University of New York at Stony Brook and became Distinguished Professor and Chairman of the Department of Biochemistry and Cell Biology, a title he still holds today. In 1990 he founded and became Director of the Institute for Cell and Developmental Biology at Stony Brook. Lennarz continues to focus on glycoproteins, and his more recent efforts have been on the structure, biosynthesis, and function of cell surface glycoproteins and the role of cell surface proteins in fertilization and embryonic development in the sea urchin and frog. Currently, he is studying the steps involved in glycoprotein synthesis, including N-glycosylation and protein folding, as well as the functions of the glycan chains. Lennarz served as president of the American Society for Biochemistry and Molecular Biology in 1989 and was also president of both the Biochemistry Chairman's Organization and the Society for Glycobiology. He was awarded the Society for Glycobiology's Karl Meyer Award in 2004. Lennarz was a member of the Executive Committee of the International Union of Biochemistry and Molecular Biology for almost a decade. He served as co-editor-in-chief for the Encyclopedia of Biological Chemistry and was a member of the editorial board for Biochemical and Biophysical Research Communications. He was elected to the National Academy of Sciences in 1989.