William J. Lennarz

Ph.D. University of Illinois
Distinguished Professor and Chairman, Department of Biochemistry and Cell Biology
Director, Institute for Cell and Developmental Biology

Cell and Biology Brochure

Research Interests: Biosynthesis and catabolism of glycoproteins; role of cell surface glycoproteins in fertilization and early development.

Our laboratory is interested in understanding several steps involved in glycoprotein synthesis, including N-glycosylation and protein folding, as well as the functions of the glycan chains. We are using yeast, a simple eukaryotic organism that can be genetically manipulated, to study glycoprotein assembly. More specifically, we are investigating the enzymatic processes of oligosaccharide addition and removal that occur in nascent polypeptides and misfolded glycoproteins, respectively ( fig.1 ). Evidence has been obtained that the enzyme PNGase associates with the proteasome before or after proteolysis of glycoproteins. In addition, PDI, the enzyme that catalyzes folding and disulfide bond formation in glycoproteins, is being studied ( fig.2 ). With respect to the function(s) of oligosaccharide chains, glycoproteins have also been shown to be involved in steps in fertilization in the sea urchin and the frog ( fig.3 ). Egg receptors for sperm have been characterized and cloned in both systems ( fig.4 ).

1. Tian, Jingdong, Gong, Hui, Thomsen, Gerald H. and Lennarz, William J., Xenopus laevis sperm receptor gp69/64 glycoprotein is a homolog of the mammalian sperm receptor ZP2. Proc. Natl. Acad. Sci. 96, 829-834 (1999).
   
2. Yan, Qi, Prestwich, Glenn D. and Lennarz, William J., The Ost1p Subunit of Yeast Oligosaccharyl Transferase Recognizes the Peptide Glycosylation Site Sequence, -Asn-X-Ser/Thr-. J. Biol. Chem. 274, 5021-5025 (1999).
   
3. Yan, Qi and Lennarz, William J., Oligosaccharyltransferase: A Complex Multisubunit Enzyme of the Endoplasmic Reticulum. Biochem. Biophys. Res. Commun. 266, 684-689 (1999).
   
4. Suzuki, Tadashi and Lennarz, William J., In Yeast the Export of Small Glycopeptides from the Endoplasmic Reticulum into the Cytosol Is Not Affected by the Structure of Their Oligosaccharide Chains. Glycobiology 10, 51-58 (2000).
   
5. Park, Hangil and Lennarz, William J., Evidence for Interaction of Yeast Protein Kinase C with Several Subunits of Oligosaccharyl Transferase. Glycobiology 10, 737-744 (2000).
   
6. Kim, Hyun, Park, Hangil, Montalvo, Lucy and Lennarz, William J., Studies on the Role of the Hydrophobic Domain of Ost4p in Interactions with other Subunits, of Yeast Oligosaccharyl Transferase. Proc. Natl. Acad. Sci. 97, 1516-1520 (2000).
   
7. Suzuki, Tadashi, Park, Hangil, Hollingsworth, Nancy M., Sternglanz, Rolf and Lennarz, William J., PNG1, a Yeast Gene Encoding a Highly Conserved Peptide:N-glycanase Involved in Protein Degradation. J. Cell Biol. 149, 1039-1051 (2000).
   
8. Hirohashi, N. and Lennarz, W. J., The Role of a Vitelline Layer-Associated 350 kDa Glycoprotein in Controlling Species Specific Gamete Interaction in the Sea Urchin. Develop. Growth Differ. 43, 247-255 (2001).
   
9. Katiyar, Samiksha, Till, Elizabeth A. and Lennarz, William J., Studies on the Function of Yeast Protein Disulfide Isomerase in Renaturation of Proteins. Biochim. et Biophys. Acta 47-56 (2001).
   
10. Suzuki, T., Park, H., Kwofie, M. A. and Lennarz, W. J., Rad23 Provides a Link between the Png1 Deglycosylating Enzyme Protein and the 26S Proteasome in Yeast. J. Biol. Chem. 276, 21601-21607 (2001).
    
11. Park, H., Suzuki, T., Lennarz, W. J., Identification of Proteins that interact with Mammalian peptide: N-glycanase and implicate this hydrolase in the proteasome-dependent pathway for protein degradation. PNAS. Vol. 98 1163-1168 (2001).
    
12. Suzuki, T., Park, H., Till, E. A., Lennarz, W. J., The PUB domain: a putative protein-protein interaction domain implicated in the ubiquitin-proteasome pathway. Biochem. Biopys. Res. Commun. 287, 1083-7. (2001)
    
13. Katiyar S., Suzuki, T., Balgobin, B. J., and Lennarz, W. J., Site-directed Mutagenesis Study of Yeast Peptide: N-Glycanase. Insight into the Reaction Mechanism of Deglycosylation. J. Biol. Chem. 277, 12953-9 (2002).
    
14. Suzuki, T., and Lennarz, W. J. Glycopeptide export from the endoplasmic reticulum into cytosol is mediated by distinct mechanism from that for export of misfolded glycoprotein. Glycobiology 12, 803-811 (2002).
    
15. Suzuki, T., Park, H. and Lennarz, W. J. Cytoplasmic Peptide:N:glycanase (PNGase) in Eukaryotic Cells: Occurrence, Primary Structure, and Potential Functions. FASEB J. 16: 635-641 (2002).
    
16. Yan, Q. and Lennarz, W. J. Studies on the Function of Oligosaccharyl Transferase Subunits. Stt3p Is Directly Involved in the Glycosylation Process. J. Biol. Chem. 277; 47692-700 (2002).
    
17. Yan, Q. and Lennarz W. J. Studies on the function of oligosaccharyl transferase subunits: A glycosylatable photoprobe binds to the lumenal domain of Ostlp. Proc. Natl. Acad. Sci. U.S.A. 99,15994-9 (2002).