Molecular Mechanisms of Receptor-Mediated Endocytosis in the Renal Proximal Tubular Epithelium

Figure 1

Megalin and its associated molecules involved in receptor-mediated endocytosis in PTEC. On the apical membrane of PTEC, various molecules are involved in the process of receptor-mediated endocytosis. Megalin, playing a central role in the process, cooperates with other membrane proteins such as the cubilin-amnionless complex (CUBAM), NHE3, and ClC5. Megalin and CUBAM directly bind a variety of ligands, whereas NHE3 and ClC5 are involved in endosomal acidification, which is important for further processing of endocytosed proteins. Megalin also interacts with intracellular adaptor proteins such as ARH, Dab2, and GIPC. Dab2 binds to motor proteins, myosin VI, and NMHC IIA, which may mediate endocytic trafficking of the molecular complexes through actin filaments. The cytoplasmic tail of megalin is released from the membrane by 𝛾-secretase and is involved in intracellular signal transduction.