An Endocytic Receptor, Megalin-Ligand Interactions: Effects of Glycosylation

Abstract

Incorporating substances from outside across plasma membranes is an essential process for cells. Receptor-mediated endocytosis plays important roles for uptake and subsequent degradation and processing of nutrients and vitamins. Megalin is a multi-ligand endocytic receptor that contributes to absorption of low molecular weight proteins on the cell surface. Megalin is a 600 kDa single-spanning transmembrane glycoprotein. It has a large extracellular domain in the N-terminus that contains four ligand-binding regions. Megalin binds with functionally and structurally distinct proteins (e.g., vitamin-binding proteins, carrier proteins and hormones) and chemical drugs (e.g., aminoglycosides) as ligands. Through the uptake of ligands, megalin mediates physiological functions in the body. Although megalin is highly glycosylated and the glycan structures have been analyzed using mass spectrometry, little has been known about the function of glycan on megalin. This article introduces the function of endocytosis mediated by megalin under physiological and pathological conditions and the effects of glycosylation of megalin on ligand-binding activity as function of glycans.