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The epithelial-specific adaptor AP1B mediates post-endocytic recycling to the basolateral membrane

Nature Cell Biology volume 4, pages 605–609 (2002)Cite this article

Abstract

To perform vectorial secretory and transport functions that are critical for the survival of the organism, epithelial cells sort plasma membrane proteins into polarized apical and basolateral domains1,2. Sorting occurs post-synthetically, in the trans Golgi network (TGN) or after internalization from the cell surface in recycling endosomes, and is mediated by apical and basolateral sorting signals embedded in the protein structure3,4. Basolateral sorting signals include tyrosine motifs in the cytoplasmic domain that are structurally similar to signals involved in receptor internalization by clathrin-coated pits5,6. Recently, an epithelial-specific adaptor protein complex, AP1B, was identified7,8. AP-1B recognizes a subset of basolateral tyrosine motifs through its μ1B subunit7,8. Here, we characterized the post-synthetic and post-endocytic sorting of the fast recycling low density lipoprotein receptor (LDLR) and transferrin receptor (TfR) in LLC-PK1 cells, which lack μ1B and mis-sort both receptors to the apical surface8. Targeting and recycling assays in LLC-PK1 cells, before and after transfection with μ1B, and in MDCK cells, which express μ1B constitutively, suggest that AP1B sorts basolateral proteins post-endocytically.

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Figure 1: μ1B colocalizes well with internalized Tf–Alexa 488 and γ-adaptin, and poorly with TGN marker TGN38.
Figure 2: LDL receptor is targeted basolaterally after synthesis in MDCK, LLC-PK1 and LLC-PK1-μ1B cells.
Figure 3: Endocytic-deficient LDLR-A18 is targeted to basolateral membranes in LLC-PK1 cells.
Figure 4: Expression of μ1B promotes basolateral targeting of Tf in LLC-PK1 cells.

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Acknowledgements

This work was supported by National Institutes of Health grants GM34107 and EY08538 and by a Jules and Doris Stein Professorship from the Research to Prevent Blindness Foundation to E.R.B., and by NIH grants DK-52852 and DK-57689 to T.E.M. We thank I. Mellman, H. Fölsch and J. Bonifacino for providing several constructs and antibodies. We thank I. Mellman and members of the Rodriguez-Boulan laboratory for critically reading the manuscript.

Author information

Authors and Affiliations

  1. Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Ave., New York, 10021, NY, USA

    Yunbo Gan & Enrique Rodriguez-Boulan

  2. Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Ave., New York, 10021, NY, USA

    Timothy E. McGraw

  3. Department of Cell Biology, Weill Medical College of Cornell University, 1300 York Ave., New York, 10021, NY, USA

    Enrique Rodriguez-Boulan

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  1. Yunbo Gan
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Correspondence to Enrique Rodriguez-Boulan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

Figure S1. Double immunofluorescence localization of µ1B and endosomal markers rab-5 and rab 11. (PDF 499 kb)

Figure S2. LLC-PK1 monolayers on filters are impermeant to antibodies.

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Gan, Y., McGraw, T. & Rodriguez-Boulan, E. The epithelial-specific adaptor AP1B mediates post-endocytic recycling to the basolateral membrane. Nat Cell Biol 4, 605–609 (2002). https://doi.org/10.1038/ncb827

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