title: Galectin-4-mediated transcytosis of transferrin receptor.
abstract: Some native epithelia, for example, retinal pigment epithelium (RPE) and kidney proximal tubule (KPT), constitutively lack the basolateral sorting adaptor AP-1B; this results in many basolateral plasma membrane proteins being repositioned to the apical domain, where they perform essential functions for their host organs. We recently reported the underlying apical polarity reversal mechanism: in the absence of AP-1B-mediated basolateral sorting, basolateral proteins are shuttled to the apical plasma membrane through a transcytotic pathway mediated by the plus-end kinesin KIF16B. Here, we demonstrate that this apical transcytotic pathway requires apical sorting of basolateral proteins, which is mediated by apical signals and galectin-4. Using RPE and KPT cell lines, and AP-1B-knockdown MDCK cells, we show that mutation of the N-glycan linked to N727 in the basolateral marker transferrin receptor (TfR) or knockdown of galectin-4 inhibits TfR transcytosis to apical recycling endosomes and the apical plasma membrane, and promotes TfR lysosomal targeting and subsequent degradation. Our results report a new role of galectins in basolateral to apical epithelial transcytosis.
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Andres E
authors.initials: AE
authors.lastname: Perez Bay
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Schreiner
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Benedicto
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA boulan@med.cornell.edu.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Rodriguez-Boulan
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000235:genetics / Q000378:metabolism*; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity / Q000235:genetics; D004285:Dogs; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D037541:Galectin 4 / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D009154:Mutation / Q000235:genetics; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D057900:Transcytosis / Q000235:genetics
chemical_list: C439126:AP1B1 protein, human; D033961:Adaptor Protein Complex 1; D033966:Adaptor Protein Complex beta Subunits; D037541:Galectin 4; D021382:Protein Sorting Signals; D011990:Receptors, Transferrin
keywords: Galectin; Glycan; Rab11a; Transcytosis; Transferrin receptor