title: The Scribble polarity protein stabilizes E-cadherin/p120-catenin binding and blocks retrieval of E-cadherin to the Golgi.
abstract: Several polarity proteins, including Scribble (Scrb) have been implicated in control of vesicle traffic, and in particular the endocytosis of E-cadherin, but through unknown mechanisms. We now show that depletion of Scrb enhances endocytosis of E-cadherin by weakening the E-cadherin-p120catenin interaction. Unexpectedly, however, the internalized E-cadherin is not degraded but accumulates in the Golgi apparatus. Silencing p120-catenin causes degradation of E-cadherin in lysosomes, but degradation is blocked by the co-depletion of Scrb, which diverts the internalized E-cadherin to the Golgi. Loss of Scrb also enhances E-cadherin binding to retromer components, and retromer is required for Golgi accumulation of Scrb, and E-cadherin stability. These data identify a novel and unanticipated function for Scrb in blocking retromer-mediated diversion of E-cadherin to the Golgi. They provide evidence that polarity proteins can modify the intracellular itinerary for endocytosed membrane proteins.
authors.affiliation: Department of Microbiology, Ctr for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors.forename: Madhura
authors.initials: M
authors.lastname: Lohia
authors.forename: Yi
authors.initials: Y
authors.lastname: Qin
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D004705:Endocytosis; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D000095002:Delta Catenin; C000722347:CTNND1 protein, human