Mannose Receptor-Mediated Regulation of Serum Glycoprotein Homeostasis

TLDR

Carbohydrates act as tags that mark circulatory glycoproteins for rapid clearance. The study aims to determine whether the mannose receptor regulates glycoprotein clearance. To test this, the authors generated mice lacking the mannose receptor. MR‑deficient mice fail to clear mannose‑ or N‑acetylglucosamine‑bearing glycoproteins, exhibit elevated lysosomal hydrolases and increased levels of four inflammation‑associated proteins, indicating that the mannose receptor is essential for maintaining serum glycoprotein homeostasis.

Abstract

Carbohydrates are thought to function as tags that mark circulatory glycoproteins for rapid clearance. To examine the role of the mannose receptor (MR) in glycoprotein clearance, we generated mice genetically deficient in MR. MR −/− mice were defective in clearing proteins bearing accessible mannose and N -acetylglucosamine residues and had elevated levels of eight different lysosomal hydrolases. Proteomic analysis of MR −/− and control mouse sera showed that an additional 4 out of 52 proteins identified were elevated in MR −/− serum. Each of these is up-regulated during inflammation and wound healing. Thus, MR appears to operate as an essential regulator of serum glycoprotein homeostasis.