Rab11 in recycling endosomes regulates the sorting and basolateral transport of E-cadherin.
E-cadherin plays an essential role in cell polarity and cell-cell adhesion; however, the pathway for delivery of E-cadherin to the basolateral membrane of epithelial cells has not been fully characterized. We first traced the post-Golgi, exocytic transport of GFP-tagged E-cadherin (Ecad-GFP) in unpolarized cells. In live cells, Ecad-GFP was found to exit the Golgi complex in pleiomorphic tubulovesicular carriers, which, instead of moving directly to the cell surface, most frequently fused with an intermediate compartment, subsequently identified as a Rab11-positive recycling endosome. In MDCK cells, basolateral targeting of E-cadherin relies on a dileucine motif. Both E-cadherin and a targeting mutant, DeltaS1-E-cadherin, colocalized with Rab11 and fused with the recycling endosome before diverging to basolateral or apical membranes, respectively. In polarized and unpolarized cells, coexpression of Rab11 mutants disrupted the cell surface delivery of E-cadherin and caused its mistargeting to the apical membrane, whereas apical DeltaS1-E-cadherin was unaffected. We thus demonstrate a novel pathway for Rab11 dependent, dileucine-mediated, mu1B-independent sorting and basolateral trafficking, exemplified by E-cadherin. The recycling endosome is identified as an intermediate compartment for the post-Golgi trafficking and exocytosis of E-cadherin, with a potentially important role in establishing and maintaining cadherin-based adhesion.
Lock
John G
JG
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Stow
Jennifer L
JL
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D011992:Endosomes / Q000378:metabolism*; D005089:Exocytosis; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D015820:Cadherins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins