The Scribble polarity protein stabilizes E-cadherin/p120-catenin binding and blocks retrieval of E-cadherin to the Golgi

PLoS One. 2012;7(11):e51130. doi: 10.1371/journal.pone.0051130. Epub 2012 Nov 30.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Catenins / metabolism*
  • Cell Nucleus / metabolism
  • Cell Polarity*
  • Delta Catenin
  • Endocytosis
  • Golgi Apparatus / metabolism*
  • Humans
  • Lysosomes / metabolism
  • Madin Darby Canine Kidney Cells
  • Membrane Proteins / deficiency
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Protein Binding
  • Protein Stability
  • Protein Transport
  • Vesicular Transport Proteins / metabolism

Substances

  • Cadherins
  • Catenins
  • Membrane Proteins
  • Vesicular Transport Proteins
  • Delta Catenin
  • CTNND1 protein, human