Galectin-4-mediated transcytosis of transferrin receptor.
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.
['Perez Bay|Andres E|AE|', 'Schreiner|Ryan|R|', 'Benedicto|Ignacio|I|', 'Rodriguez-Boulan|Enrique J|EJ|']
D033961:Adaptor Protein Complex 1 D033966:Adaptor Protein Complex beta Subunits D000818:Animals D002460:Cell Line D002462:Cell Membrane D016764:Cell Polarity D004285:Dogs D011992:Endosomes D004847:Epithelial Cells D037541:Galectin 4 D055785:Gene Knockdown Techniques D006801:Humans D008247:Lysosomes D061985:Madin Darby Canine Kidney Cells D009154:Mutation D021382:Protein Sorting Signals D021381:Protein Transport D011990:Receptors, Transferrin D057900:Transcytosis
Transcytosis Transferrin receptor Galectin Glycan Rab11a