The fast-recycling receptor Megalin defines the apical recycling pathway of epithelial cells

• Published in: Nature communications Vol. 7; no. 1; p. 11550
• Main Authors: Perez Bay, Andres E, Schreiner, Ryan, Benedicto, Ignacio, Paz Marzolo, Maria, Banfelder, Jason, Weinstein, Alan M, Rodriguez-Boulan, Enrique J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 16.05.2016; Nature Portfolio
• Subjects: Animals; Cell Polarity; Dogs; Endocytosis; Endosomes - metabolism; Epithelial Cells - cytology; Epithelial Cells - metabolism; Kinetics; Ligands; Low Density Lipoprotein Receptor-Related Protein-2 - metabolism; Madin Darby Canine Kidney Cells; Microtubules - metabolism; Models, Biological; Physiology; Proteins; Proteolysis; rab GTP-Binding Proteins - metabolism; Recycling; Chile; New York; United States > US
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11550

The basolateral recycling and transcytotic pathways of epithelial cells were previously defined using markers such as transferrin (TfR) and polymeric IgA (pIgR) receptors. In contrast, our knowledge of the apical recycling pathway remains fragmentary. Here we utilize quantitative live-imaging and mathematical modelling to outline the recycling pathway of Megalin (LRP-2), an apical receptor with key developmental and renal functions, in MDCK cells. We show that, like TfR, Megalin is a long-lived and fast-recycling receptor. Megalin enters polarized MDCK cells through segregated apical sorting endosomes and subsequently intersects the TfR and pIgR pathways at a perinuclear Rab11-negative compartment termed common recycling endosomes (CRE). Whereas TfR recycles to the basolateral membrane from CRE, Megalin, like pIgR, traffics to subapical Rab11-positive apical recycling endosomes (ARE) and reaches the apical membrane in a microtubule- and Rab11-dependent manner. Hence, Megalin defines the apical recycling pathway of epithelia, with CRE as its apical sorting station.