title: The fast-recycling receptor Megalin defines the apical recycling pathway of epithelial cells.
abstract: 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.
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Andres E
authors.initials: AE
authors.lastname: Perez Bay
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Schreiner
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Benedicto
authors.affiliation: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Avenida del Libertador Bernardo O'Higgins 340, 8331010 Santiago, Chile.
authors.forename: Maria
authors.initials: M
authors.lastname: Paz Marzolo
authors.affiliation: Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Banfelder
authors.affiliation: Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Weinstein
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.|Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Rodriguez-Boulan
mesh_terms: D000818:Animals; D016764:Cell Polarity; D004285:Dogs; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D007700:Kinetics; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D059748:Proteolysis; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins