Research Abstract:
Post-translational modification of proteins with carbohydrate chains of defined structure provides a mechanism to vastly expand the repertoire of gene products that are produced and to regulate their biologic activity. One such system we have defined is the reproductive glycoprotein hormones luteinizing hormone (LH) and the prolactin-like proteins (PLPs). We have shown that they bear unique carbohydrate structures that help regulate the production of steroid hormones (estrogens, androgens, and progesterone) needed for sexual reproduction and the maintenance of pregnancy. Carbohydrate-specific receptors regulate the circulatory half lives of these glycosylated hormones in the blood and thus determine their concentration and potency. Expression of both the transferases that synthesize these unique carbohydrate structures and of the carbohydrate-specific receptors are developmentally and hormonally regulated in a tissue and cell specific manner. By generating mice that are either deficient in enzymes that synthesize the carbohydrate structures critical for the biologic activity of glycosylated hormones or deficient in carbohydrate-specific receptors, we are further defining the roles played by these unique carbohydrates in vivo. We have now found that these same carbohydrates and receptors play a role in other systems, such as in regulation of the levels of plasma glycoproteins during tissue injury and inflammation.
Selected Publications:
Steirer LM, Park EI, Townsend RR, Baenziger JU. The asialoglycoprotein receptor regulates levels of plasma glycoproteins terminating with sialic acidalpha 2,6galactose. J Biol Chem 2009 284: 3777-3783. PMCID: PMC2635048
Mi Y, Fiete D, Baenziger JU. Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering carbohydrate structures of luteinizing hormone in mice. J Clin Invest 2008 118: 1815-1824. PMCID: PMC2323185
Miller E, Fiete D, Blake NM, Beranek M, Oates EL, Mi Y, Roseman DS, Baenziger JU. A necessary and sufficient determinant for protein-selective glycosylation in vivo. J Biol Chem 2008 283: 1985-1991. PMID #18048353
Fiete D, Mi Y, Oates EL, Beranek MC, Baenziger JU. N-linked oligosaccharides on the low density lipoprotein homolog SorLA/LR11 are modified with terminal GalNAc-4-SO4 inn kidney and brain. J Biol Chem 2007 282: 1873-1881. PMID #17121844
Park EI, Mi Y, Unverzagt C, Gabius HJ and Baenziger JU. The Asialoglycoprotein receptor clears glycoconjugates terminating with Sialic acid alpha-2,6GalNAc. Proc Natl Acad Sci USA 2005 102: 17125-17129. PMID #16286643
Last Updated: 08/12/2009 |