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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mi, Yiling Lin, Angela Baenziger, Jacques U. Fiete, Dorothy Steirer, Lindsay |
| Description | Author Affiliation: Mi Y ( From the Department of Pathology, Washington University School of Medicine in St. Louis, St. Louis, Missouri 63110.) |
| Abstract | The rate at which glycoproteins are cleared from the circulation has a critical impact on their biologic activity in vivo. We have shown that clearance rates for glycoproteins such as luteinizing hormone (LH) that undergo regulated release into the circulation determine their potency. Two highly abundant, carbohydrate-specific, endocytic receptors, the asialoglycoprotein receptor (ASGR) and the mannose receptor (ManR) are expressed in the liver by parenchymal and sinusoidal endothelial cells, respectively. We demonstrate that the ManR mediates the clearance of glycoproteins such as LH that bear N-linked glycans terminating with ß1,4-linked GalNAc-4-SO4, as well as glycoproteins bearing glycans that terminate with Man. Steady state levels of mRNA encoding the ASGR and the ManR are regulated by progesterone in pregnant mice, reaching maximal levels on day 12.5 of pregnancy. Protein expression and glycan-specific binding activity also increase in the livers of pregnant mice. In contrast, ManR mRNA, but not ASGR mRNA, decreases in male mice at the time of sexual maturation. We show that levels of ManR and ASGR expression control the clearance rate for glycoproteins bearing recognized glycans. Thus, reduced expression of the ManR at the time of sexual maturation will increase the potency of LH in vivo, whereas increased expression during pregnancy will reduce LH potency until progesterone and receptor levels fall prior to parturition. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 17 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-04-25 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Asialoglycoprotein Receptor Metabolism Glycoproteins Mannose Reproduction Animals Genetics DNA Primers Mice Pregnancy RNA, Messenger Real-Time Polymerase Chain Reaction Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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