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

• Published in: Nature communications 2016-05, Vol.7 (1), p.11550-11550, Article 11550
• Main Authors: Perez Bay, Andres E., Schreiner, Ryan, Benedicto, Ignacio, Paz Marzolo, Maria, Banfelder, Jason, Weinstein, Alan M., Rodriguez-Boulan, Enrique J.
• Format: Article
• Language: English
• Subjects: 14; 14/1; 14/19; 14/34; 14/63; 631/45/612/1237; 631/80/86; Animals; Cell Polarity; Dogs; Endocytosis; Endosomes - metabolism; Epithelial Cells - cytology; Epithelial Cells - metabolism; Humanities and Social Sciences; Kinetics; Ligands; Low Density Lipoprotein Receptor-Related Protein-2 - metabolism; Madin Darby Canine Kidney Cells; Microtubules - metabolism; Models, Biological; multidisciplinary; Physiology; Proteins; Proteolysis; rab GTP-Binding Proteins - metabolism; Recycling; Science; Science (multidisciplinary)
• 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. Basolateral recycling and transcytotic pathways in epithelial cells are defined by specific markers, however the apical recycling pathway is poorly understood. Perez Bay et al . show that Megalin is a marker for this pathway, which intersects with the other routes in shared perinuclear recycling endosomes.