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

Author

Listed:
  • Andres E. Perez Bay

    (Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University)

  • Ryan Schreiner

    (Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University)

  • Ignacio Benedicto

    (Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University)

  • Maria Paz Marzolo

    (Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile)

  • Jason Banfelder

    (Weill Medical College of Cornell University)

  • Alan M. Weinstein

    (Weill Medical College of Cornell University)

  • Enrique J. Rodriguez-Boulan

    (Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University
    Weill Medical College of Cornell University)

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.

Suggested Citation

  • Andres E. Perez Bay & Ryan Schreiner & Ignacio Benedicto & Maria Paz Marzolo & Jason Banfelder & Alan M. Weinstein & Enrique J. Rodriguez-Boulan, 2016. "The fast-recycling receptor Megalin defines the apical recycling pathway of epithelial cells," Nature Communications, Nature, vol. 7(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11550
    DOI: 10.1038/ncomms11550
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